Mixto Vs Peri

Combined spinal-epidural versus epidural analgesia in labour
(Review)
Simmons SW, Taghizadeh N, Dennis AT, Hughes D, Cyna AM
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2012, Issue 10
http://www.thecochranelibrary.com
Combined spinal-epidural versus epidural analgesia in labour (Review)

Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Figure 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
Analysis 1.1. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 1 Time from first injection to
effective analgesia (minutes). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
Analysis 1.3. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 3 Need for rescue analgesia. 70
Analysis 1.5. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 5 Number of women who
mobilise. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
Analysis 1.6. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 6 Post dural puncture
headache. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
Analysis 1.7. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 7 Known dural tap. . . 73
Analysis 1.8. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 8 Number of women requiring
blood patch for post dural puncture headache. . . . . . . . . . . . . . . . . . . . . . . 74
Analysis 1.9. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 9 Pruritus. . . . . . 75
Analysis 1.10. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 10 Urinary retention. . 76
Analysis 1.11. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 11 Nausea/vomiting. . 77
Analysis 1.12. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 12 Hypotension. . . 78
Analysis 1.13. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 13 Respiratory depression. 79
Analysis 1.14. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 14 Headache (any). . 80
Analysis 1.15. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 15 Sedation. . . . . 80
Analysis 1.16. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 16 Labour augmentation
required. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Analysis 1.17. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 17 Augmentation after
analgesia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
Analysis 1.18. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 18 Normal delivery. . 83
Analysis 1.19. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 19 Instrumental delivery. 84
Analysis 1.20. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 20 Caesarean section. . 85
Analysis 1.21. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 21 Umbilical arterial pH. 86
Analysis 1.22. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 22 Umbilical venous pH. 86
Analysis 1.24. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 24 Apgar score < 7 at 5
minutes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
Analysis 1.25. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 25 Apgar score < 8 at 5
minutes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
Analysis 1.26. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 26 Number admitted to
neonatal unit. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
Analysis 2.1. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 1 Time from first injection to
effective analgesia (minutes). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
Combined spinal-epidural versus epidural analgesia in labour (Review) i
Analysis 2.2. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 2 Number of women with
effective analgesia 10 minutes after first injection. . . . . . . . . . . . . . . . . . . . . . 90
Analysis 2.3. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 3 Need for rescue analgesia. 91
Analysis 2.4. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 4 Number of women satisfied
with analgesia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
Analysis 2.5. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 5 Number of women who
mobilise. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
Analysis 2.6. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 6 Post dural puncture
headache. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Analysis 2.7. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 7 Known dural tap. . . 95
Analysis 2.8. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 8 Number of women requiring
blood patch for post dural puncture headache. . . . . . . . . . . . . . . . . . . . . . . 96
Analysis 2.9. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 9 Pruritus. . . . . . 97
Analysis 2.10. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 10 Urinary retention. . 98
Analysis 2.11. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 11 Nausea/vomiting. . 99
Analysis 2.12. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 12 Hypotension. . . . 100
Analysis 2.13. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 13 Respiratory depression. 101
Analysis 2.14. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 14 Headache (any). . . 102
Analysis 2.16. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 16 Labour augmentation
required. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
Analysis 2.18. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 18 Normal delivery. . . 104
Analysis 2.19. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 19 Instrumental delivery. 105
Analysis 2.20. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 20 Caesarean section. . 107
Analysis 2.21. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 21 Umbilical arterial pH. 109
Analysis 2.22. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 22 Umbilical venous pH. 110
Analysis 2.23. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 23 Umbilical cord pH. . 111
Analysis 2.24. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 24 Apgar score < 7 at 5
minutes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
Analysis 2.25. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 25 Apgar score < 8 at 5
minutes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
Analysis 2.26. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 26 Number admitted to
neonatal unit. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . . 118
INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
Combined spinal-epidural versus epidural analgesia in labour (Review) ii

[Intervention Review]
Scott W Simmons1 , Neda Taghizadeh1 , Alicia T Dennis2 , Damien Hughes3 , Allan M Cyna4
1 Department of Anaesthesia, Mercy Hospital for Women, Heidelberg, Australia. 2 Department of Anaesthesia, Royal Women’s Hospital,
Parkville, Australia. 3 Department of Obstetrics and Gynaecology Anaesthesia, Women’s and Children’s Hospital, Adelaide, Australia.
4 Department of Women’s Anaesthesia, Women’s and Children’s Hospital, Adelaide, Australia
Contact address: Scott W Simmons, Department of Anaesthesia, Mercy Hospital for Women, 163 Studley Road, Heidelberg, Victoria,
3084, Australia. ssimmons@mercy.com.au. swsimmo@bigpond.net.au.
Editorial group: Cochrane Pregnancy and Childbirth Group.

Publication status and date: New search for studies and content updated (no change to conclusions), published in Issue 10, 2012.
Review content assessed as up-to-date: 1 March 2012.
Citation: Simmons SW, Taghizadeh N, Dennis AT, Hughes D, Cyna AM. Combined spinal-epidural versus epidural analgesia in
labour. Cochrane Database of Systematic Reviews 2012, Issue 10. Art. No.: CD003401. DOI: 10.1002/14651858.CD003401.pub3.
ABSTRACT
Background
Traditional epidural techniques have been associated with prolonged labour, use of oxytocin augmentation and increased incidence
of instrumental vaginal delivery. The combined spinal-epidural (CSE) technique has been introduced in an attempt to reduce these
adverse effects. CSE is believed to improve maternal mobility during labour and provide more rapid onset of analgesia than epidural
analgesia, which could contribute to increased maternal satisfaction.
Objectives
To assess the relative effects of CSE versus epidural analgesia during labour.
Search methods
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (28 September 2011) and reference lists of retrieved
studies. We updated the search on 30 June 2012 and added the results to the awaiting classification section.
Selection criteria
All published randomised controlled trials (RCTs) involving a comparison of CSE with epidural analgesia initiated for women in the
first stage of labour. Cluster-randomised trials were considered for inclusion. Quasi RCTs and cross-over trials were not considered for
inclusion in this review.
Data collection and analysis
Three review authors independently assessed the trials identified from the searches for inclusion, assessed trial quality and extracted the
data. Data were checked for accuracy.
Main results
Twenty-seven trials involving 3274 women met our inclusion criteria. Twenty-six outcomes in two sets of comparisons involving CSE
versus traditional epidurals and CSE versus low-dose epidural techniques were analysed.
Of the CSE versus traditional epidural analyses five outcomes showed a significant difference. CSE was more favourable in relation to
speed of onset of analgesia from time of injection (mean difference (MD) -2.87 minutes; 95% confidence interval (CI) -5.07 to -0.67;
Combined spinal-epidural versus epidural analgesia in labour (Review) 1
two trials, 129 women); the need for rescue analgesia (risk ratio (RR) 0.31; 95% CI 0.14 to 0.70; one trial, 42 women); urinary retention
(RR 0.86; 95% CI 0.79 to 0.95; one trial, 704 women); and rate of instrumental delivery (RR 0.81; 95% CI 0.67 to 0.97; six trials,
1015 women). Traditional epidural was more favourable in relation to umbilical venous pH (MD -0.03; 95% CI -0.06 to -0.00; one
trial, 55 women). There were no data on maternal satisfaction, blood patch for post dural puncture headache, respiratory depression,
umbilical cord pH, rare neurological complications, analgesia for caesarean section after analgesic intervention or any economic/use
of resources outcomes for this comparison. No differences between CSE and traditional epidural were identified for mobilisation in
labour, the need for labour augmentation, the rate of caesarean birth, incidence of post dural puncture headache, maternal hypotension,
neonatal Apgar scores or umbilical arterial pH.
For CSE versus low-dose epidurals, three outcomes were statistically significant. Two of these reflected a faster onset of effective analgesia
from time of injection with CSE and the third was of more pruritus with CSE compared to low-dose epidural (average RR 1.80;
95% CI 1.22 to 2.65; 11 trials, 959 women; random-effects, T² = 0.26, I² = 84%). There was no significant difference in maternal
satisfaction (average RR 1.01; 95% CI 0.98 to 1.05; seven trials, 520 women; random-effects, T² = 0.00, I² = 45%). There were no data
on respiratory depression, maternal sedation or the need for labour augmentation. No differences between CSE and low-dose epidural
were identified for need for rescue analgesia, mobilisation in labour, incidence of post dural puncture headache, known dural tap, blood
patch for post dural headache, urinary retention, nausea/vomiting, hypotension, headache, the need for labour augmentation, mode
of delivery, umbilical pH, Apgar score or admissions to the neonatal unit.
Authors’ conclusions
There appears to be little basis for offering CSE over epidurals in labour, with no difference in overall maternal satisfaction despite
a slightly faster onset with CSE and conversely less pruritus with low-dose epidurals. There was no difference in ability to mobilise,
maternal hypotension, rate of caesarean birth or neonatal outcome. However, the significantly higher incidence of urinary retention,
rescue interventions and instrumental deliveries with traditional techniques would favour the use of low-dose epidurals. It is not possible
to draw any meaningful conclusions regarding rare complications such as nerve injury and meningitis.
PLAIN LANGUAGE SUMMARY
Regional analgesia has been shown to be effective in providing pain relief in labour. Regional analgesia can be an epidural, a spinal or a
combination of the two. An epidural is when the pain-relieving drugs are injected into the part of the body which surrounds the spinal
column (epidural space). It is most common for these drugs to be infused through a very fine tube (catheter) positioned in the epidural
space. Traditionally, high concentrations of local anaesthetic drugs were used. These numbed the woman from the waist downwards
giving pain relief for most women. However, it also caused leg weakness, poor mobility and difficulty for the mother giving birth. This
led to increased instrumental vaginal births with subsequent increased bruising, pain and incontinence later on for the mother. More
recently with epidurals, low-dose local anaesthetic drugs have been used in combination with opioid drugs. Here there is less numbing
of the woman’s legs but the opioid drugs cross the placenta and may make the baby sleepy.
A spinal is when the analgesic drugs are injected directly into the fluid surrounding the nerves in the spinal column and is quicker to take
effect than an epidural. However, because a single spinal injection is only effective for a short period of time, they are not commonly
used on their own for pain relief in labour. Also, the use of very fine catheters in the spinal space has been associated with increased
injury to nerves. Hence, the combination of a single spinal injection combined with the use of an epidural catheter for ongoing pain
relief was developed. This combined spinal-epidural was thought to have the benefits of being quicker to provide pain relief but with
no change to the incidence or severity of side effects for the mother or baby.
This review of trials compared CSE with traditional and with low-dose epidurals. There were 27 trials, involving 3274 women. The
data showed no difference in the mothers’ satisfaction between CSE and epidurals. However, CSEs had a slightly faster onset of effective
pain relief, but more women itched than with low-dose epidurals. There was no difference seen for mobility in labour, headaches,
caesarean section or adverse effects for the baby. Any differences for rare complications such as nerve injury and meningitis remain
unknown. There appears to be little difference overall between these techniques.
BACKGROUND
of action within the spinal cord and the peripheral nerve roots
This review is one in a series of Cochrane reviews examining pain (Butterworth 1998), which supply the uterus. Spinal analgesia is
management in labour. These reviews contribute to an overview not usually used as the sole technique for pain relief in labour
of systematic reviews of pain management for women in labour because of its relatively short duration. The insertion and use of
(Jones 2011b). spinal micro-catheters has previously been associated with a higher
risk of permanent neurological damage (Rigler 1991) and this
Epidural analgesia has been shown to be the most effective method
technique is not in widespread use. CSE is claimed to combine
of providing pain relief in labour (Glosten 1999) when compared
the advantages of both epidural and spinal techniques including:
with non-epidural methods (Anim-Somuah 2011; Howell 2001).
faster onset, more reliable analgesia (due to the spinal compo-
On a national level, an epidural technique is used for pain relief in
nent), minimal motor and sensory blockade, improved mobilisa-
approximately 25% of labouring women in the UK (Khor 2000;
tion (Collis 1993; Rawal 1997a), lower maternal and cord blood
NOAD 2004) and in as many as 58% in the USA (Declercq
local anaesthetic concentrations (Brown 1999), and higher patient
2002). Administration of regional analgesia traditionally involves
satisfaction (Collis 1994). Since its introduction, CSE has become
an injection of local anaesthetic through a catheter positioned
increasingly popular (Macarthur 1999; Riley 1999) and is used
in the epidural space. Epidural solutions are administered either
routinely at many institutions for obstetric analgesia (Collis 1994;
by bolus or infusion which permits analgesia to be maintained
Rawal 2000).
throughout labour. Bolus administration may be at the discretion
of the woman in labour in which case it is referred to as patient- Although all regional techniques can provide effective pain relief,
controlled epidural analgesia (PCEA). In addition, a functioning this needs to be balanced with the risk of potential adverse ef-
epidural catheter usually gives the option of providing regional fects (Bromage 1999). Complications common to both CSE and
anaesthesia for obstetric interventions such as forceps delivery or epidural analgesic techniques include failure to provide satisfactory
caesarean section, thus avoiding the risks of general anaesthesia pain relief, maternal hypotension, post dural puncture headache
(Hibbard 1996). (PDPH) (Macarthur 2009), urinary retention, itching and tran-
sient backache over the injection site. Rare serious complications
Traditional epidural techniques, employing high concentrations of
include meningitis, compression of the spinal cord from a blood
local anaesthetic (at least 0.25% bupivacaine), have been associated
clot or abscess and damage to nerve roots causing paraesthesia or
with prolonged labour, use of oxytocin augmentation and an in-
weakness. In addition, inadvertent administration of an epidural
creased incidence of instrumental vaginal delivery (Anim-Somuah
dose of local anaesthetic intravenously or intrathecally can result
2011). This is probably secondary to a dense motor block which
in convulsions or total spinal anaesthesia respectively, requiring
results in leg weakness, poor mobility, decreased pelvic muscle
resuscitation and urgent delivery (Rawal 1997a). The use of two
tone and an impaired bearing-down reflex during the delivery of
needles in CSE, one epidural and one spinal, may increase the
the baby (Thornton 2001). Newer regional techniques for labour
potential for disruption of the protective dural barrier with an
analgesia use a low concentration of local anaesthetic often in com-
associated increase in maternal complications (Macarthur 1999).
bination with an opioid. This low-dose combination appears to
Modern spinal needles are designed to minimise the incidence of
provide the excellent analgesia of higher concentrations of epidu-
PDPH (Choi 2005), which is approximately 1.5% to 2%. Epidu-
ral local anaesthetics (Akerman 1988) while maintaining motor
ral needles are not designed to enter the intrathecal space and if
function. The mother is therefore more likely to have the ability
they do so accidentally, which occurs in approximately 1.5% of
to walk during her labour or deliver without assistance (COMET
women, they are associated with an approximately 50% chance
2001a; Russell 2000).
of developing a PDPH (Macarthur 2009). This complication can
The combined spinal-epidural involves an injection of an analgesic sometimes be disabling (Weir 2000). If the headache fails to re-
or local anaesthetic drug, or both, into the intrathecal space imme- solve spontaneously an epidural blood patch is a common form of
diately before or after epidural catheter placement. A number of treatment which has been shown to be more effective than conser-
variations in the technique have been described (Cook 2000) but vative management (Boonmak 2010), providing complete relief
typically an epidural needle is first used to identify the epidural of headache at seven days in over 80% of women (van Kooten
space (Brown 1999) at the level of the third lumbar vertebra. A 2007). Although a high block may occur with spinal or epidural
smaller diameter, longer needle is then passed through the epidu- anaesthesia alone, CSE may increase the risk of this complication
ral needle lumen piercing the dura and arachnoid to allow ad- (Macarthur 1999; Rawal 1997; Shaw 2001), which can lead to
ministration of analgesic medications (e.g. opioids) into the cere- maternal hypotension, respiratory arrest or loss of consciousness.
brospinal fluid. The spinal needle is then removed and an epidural Neonatal effects such as fetal bradycardia (Nielsen 1996) or the
catheter is inserted and secured in the normal way. Further anal- need for resuscitation have been associated with the use of both
gesia usually in the form of a low-dose local anaesthetic solution CSE and epidural techniques (COMET 2001a). Differences in
combined with an opioid is then provided through the epidural the management of labour (Russell 2000) as well as differences in
catheter. Both epidural and spinal drugs are believed to access sites CSE and epidural techniques (COMET 2001a) themselves may

affect the need for other interventions during labour or delivery. • Number of women with post dural puncture headache.
• Number of women with a known dural tap.
• Number of women requiring an epidural blood patch for a
OBJECTIVES post dural puncture headache.
• Number of women with any complication requiring
To assess the relative efficacy and side effects of combined spinal- treatment/intervention specifically identified: pruritus, urinary
epidural versus epidural analgesia during labour. retention, nausea or vomiting, or both, hypotension, respiratory
depression/arrest, headache (any), sedation.
• Number of women with any other complication requiring
METHODS intervention such as fever, persistent paraesthesia, high block.
• Number of women having an instrumental delivery.
• Number of women having a caesarean section.
Criteria for considering studies for this review
For the neonate
• Number of neonates with Apgar scores less than seven at
Types of studies five minutes.
All published randomised controlled trials comparing combined • The number of neonates admitted to the neonatal unit and
spinal-epidural with epidural analgesia during labour. Cluster-ran- the reason for such admission.
domised trials were considered for inclusion. Quasi RCTs and
cross-over trials were not considered for inclusion in this review.
Economic/use of resources
• Costs of hospital stay.
Types of participants
Women having combined spinal-epidural or epidural analgesia
Secondary outcomes
commenced during the first stage of labour.
The outcomes of interest for the mother are as follows.
• Number of women requiring augmentation of labour at any
Types of interventions time.
Combined spinal-epidural analgesia compared with traditional • Number of women requiring augmentation after analgesic
and low-dose epidural analgesia. intervention.
• Number of women having a normal delivery including
vacuum extraction.
Types of outcome measures
• Number of women requiring follow-up for any reason or
with long-term outcomes, e.g. meningitis, neuropraxia, paralysis,
Primary outcomes intensive care unit admission, backache, footdrop, unresolved
post dural puncture headache.
The outcomes of interest for the mother are as follows.
• Number of women requiring general anaesthesia for
• Mean time and standard deviation from request of analgesia
caesarean section after analgesic intervention.
to the time she felt the level of pain relief was satisfactory.
• Mean time and standard deviation from first spinal or
epidural injection to the time she felt the level of pain relief was For the neonate
satisfactory. • Mean pH and standard deviation for: umbilical artery,
• Number of women after 10 minutes from the time of first umbilical vein, umbilical cord.
spinal or epidural injection experiencing satisfactory pain relief. • Number of neonates with Apgar scores less than eight at
• Number of women requiring an additional intervention for five minutes.
pain relief at any time after combined spinal-epidural (CSE)/
epidural insertion, e.g. new technique such as intravenous
Economic/use of resources
analgesia (e.g. fentanyl) replacing epidural catheter.
• Number of women satisfied with their labour analgesia. • Length of hospital stay.
• Number of women who were mobile. Maternal mobility is • The number of women re-admitted to hospital within one
defined as the mother demonstrating that she was able to walk month of being discharged home and reason for admission.
during labour on at least one occasion following the CSE or • The number of women requiring ongoing anaesthetic
epidural. follow-up following discharge from hospital.

Search methods for identification of studies Data extraction and management
We designed a form to extract data. For eligible studies, two review
authors extracted the data using the agreed form. We resolved
discrepancies through discussion or, if required, we consulted a
Electronic searches
third person. We entered data into Review Manager software (
We searched the Cochrane Pregnancy and Childbirth Group’s RevMan 2011) and checked for accuracy.
Trials Register by contacting the Trials Search Co-ordinator (28 When information regarding any of the above was unclear, we
September 2011). We updated this on 30 June 2012 and added attempted to contact authors of the original reports to provide
the results to Studies awaiting classification. further details.
The Cochrane Pregnancy and Childbirth Group’s Trials Register
is maintained by the Trials Search Co-ordinator and contains trials Assessment of risk of bias in included studies
identified from:
Two review authors independently assessed risk of bias for each
1. quarterly searches of the Cochrane Central Register of
study using the criteria outlined in the Cochrane Handbook for
Controlled Trials (CENTRAL);
Systematic Reviews of Interventions (Higgins 2011). We resolved
2. weekly searches of MEDLINE;
any disagreement by discussion or by involving a third assessor.
3. weekly searches of EMBASE;
4. handsearches of 30 journals and the proceedings of major
conferences; (1) Random sequence generation (checking for possible
5. weekly current awareness alerts for a further 44 journals selection bias)
plus monthly BioMed Central email alerts. We described for each included study the method used to generate
Details of the search strategies for CENTRAL, MEDLINE and the allocation sequence in sufficient detail to allow an assessment
EMBASE, the list of handsearched journals and conference pro- of whether it should produce comparable groups.
ceedings, and the list of journals reviewed via the current aware- We assessed the method as:
ness service can be found in the ‘Specialized Register’ section • low risk of bias (any truly random process, e.g. random
within the editorial information about the Cochrane Pregnancy number table; computer random number generator);
and Childbirth Group. • high risk of bias (any non-random process, e.g. odd or even
Trials identified through the searching activities described above date of birth; hospital or clinic record number); or
are each assigned to a review topic (or topics). The Trials Search • unclear risk of bias.
Co-ordinator searches the register for each review using the topic
list rather than keywords.
(2) Allocation concealment (checking for possible selection
bias)
We described for each included study the method used to con-
Searching other resources ceal allocation to interventions prior to assignment and assessed
We searched reference lists of retrieved studies. whether intervention allocation could have been foreseen in ad-
We did not apply any language restrictions. vance of, or during recruitment, or changed after assignment.
We assessed the methods as:
• low risk of bias (e.g. telephone or central randomisation;
consecutively numbered sealed opaque envelopes);
Data collection and analysis • high risk of bias (open random allocation; unsealed or non-
opaque envelopes, alternation; date of birth);
For the methods used when assessing the trials identified in the • unclear risk of bias.
previous version of this review, see Appendix 1.
For this update we used the following methods when assessing the
(3) Blinding of participants, personnel and outcome
reports identified by the updated search.
assessment (checking for possible performance bias or
detection bias)
We described for each included study the methods used, if any, to
Selection of studies
blind study participants and personnel from knowledge of which
Three review authors independently assessed for inclusion all the intervention a participant received. We considered studies to be
potential studies we identified as a result of the search strategy. We at low risk of bias if they were blinded, or if we judged that the
resolved any disagreement through discussion or, if required, by lack of blinding would be unlikely to affect results. We assessed
consultation with a fourth person. blinding separately for different outcomes or classes of outcomes.

We assessed the methods as: • unclear whether there is risk of other bias.
• low, high or unclear risk of bias for participants;
• low, high or unclear risk of bias for personnel;
• low, high or unclear risk of bias for outcome assessors. (7) Overall risk of bias
We made explicit judgements about whether studies are at high risk
of bias, according to the criteria given in the Cochrane Handbook for
(4) Incomplete outcome data (checking for possible attrition
Systematic Reviews of Interventions (Higgins 2011). With reference
bias due to the amount, nature and handling of incomplete
to (1) to (6) above, we assessed the likely magnitude and direction
outcome data)
of the bias and whether we considered it likely to impact on the
We described for each included study, and for each outcome or findings. We planned to explore the impact of the level of bias
class of outcomes, the completeness of data including attrition and through undertaking sensitivity analyses - see ’Sensitivity analysis’.
exclusions from the analysis. We state whether attrition and exclu-
sions were reported and the numbers included in the analysis at
each stage (compared with the total randomised participants), rea- Measures of treatment effect
sons for attrition or exclusion where reported, and whether miss-
ing data were balanced across groups or were related to outcomes.
Where sufficient information was reported, or was supplied by the Dichotomous data
trial authors, we re-included missing data in the analyses which For dichotomous data, we present results as summary risk ratio
we undertook. with 95% confidence intervals.
We assessed methods as:
• low risk of bias (e.g. no missing outcome data; missing
outcome data balanced across groups); Continuous data
• high risk of bias (e.g. numbers or reasons for missing data
For continuous data, we used the mean difference if outcomes
imbalanced across groups; ‘as treated’ analysis done with
were measured in the same way between trials. We used the stan-
substantial departure of intervention received from that assigned
dardised mean difference to combine trials that measured the same
at randomisation);
outcome, but used different methods.
• unclear risk of bias.
(5) Selective reporting (checking for reporting bias)

Unit of analysis issues
We described for each included study how we investigated the

possibility of selective outcome reporting bias and what we found.
Cluster-randomised trials
We assessed the methods as:
• low risk of bias (where it is clear that all of the study’s pre- There were no cluster-randomised trials for inclusion in this re-
specified outcomes and all expected outcomes of interest to the view.
review have been reported); We intended to include cluster-randomised trials in the analyses
• high risk of bias (where not all the study’s pre-specified along with individually randomised trials using the methods de-
outcomes have been reported; one or more reported primary scribed in the Cochrane Handbook (Higgins 2011). Their sam-
outcomes were not pre-specified; outcomes of interest are ple sizes would be adjusted using an estimate of the intracluster
reported incompletely and so cannot be used; study fails to correlation co-efficient (ICC) derived from the trial (if possible),
include results of a key outcome that would have been expected or from another source. If we used ICCs from other sources, we
to have been reported); would report this and conduct sensitivity analyses to investigate
• unclear risk of bias. the effect of variation in the ICC. If we had identified both cluster-
randomised trials and individually randomised trials, we planned
to synthesise the relevant information. We would consider it rea-
(6) Other bias (checking for bias due to problems not sonable to combine the results from both if there was little hetero-
covered by 1 to 5 above) geneity between the study designs and the interaction between the
We described for each included study any important concerns we effect of intervention and the choice of randomisation unit was
have about other possible sources of bias. considered to be unlikely.
We assessed whether each study was free of other problems that
could put it at risk of bias:
• low risk of other bias; Cross-over trials
• high risk of other bias; We did not include cross-over trials.

Dealing with missing data Where we used random-effects analyses, the results are presented
For included studies, we noted levels of attrition. We planned to as the average treatment effect with 95% confidence intervals, and
explore the impact of including studies with high levels of missing the estimates of T² and I².
data in the overall assessment of treatment effect by using sensi-
tivity analysis.
For all outcomes, we carried out analyses, as far as possible, on an Subgroup analysis and investigation of heterogeneity
intention-to-treat basis, i.e. we attempted to include all partici- If we identified substantial heterogeneity, we investigated it using
pants randomised to each group in the analyses, and analysed all
subgroup analyses and sensitivity analyses. We considered whether
participants in the group to which they were allocated, regardless
an overall summary was meaningful and, if it was, we used random-
of whether or not they received the allocated intervention. The
effects analysis to produce it.
denominator for each outcome in each trial was the number ran-
We planned, where possible, to carry out the following subgroup
domised minus any participants whose outcomes are known to be
analyses based on type of combined spinal-epidural:
missing. • Combined spinal epidural versus opioid combined spinal
epidural versus null combined spinal epidural.
Assessment of heterogeneity
We considered all outcomes in subgroup analysis.
We assessed statistical heterogeneity in each meta-analysis using
We assessed subgroup differences by interaction tests available
the T², I² and Chi² statistics. We regarded heterogeneity as sub-
within RevMan (RevMan 2011).
stantial if T² was greater than zero and either I² was greater than
30% or there was a low P value (< 0.10) in the Chi² test for het-
erogeneity.
Sensitivity analysis
We planned to carry out sensitivity analyses to explore the effect of
Assessment of reporting biases trial quality assessed by concealment of allocation, high attrition
Where there were 10 or more studies in the meta-analysis we in- rates, or both, with poor quality studies being excluded from the
vestigated reporting biases (such as publication bias) using fun- analyses in order to assess whether this made any difference to the
nel plots. We assessed funnel plot asymmetry visually, and used overall result. We also planned to explore the effects of fixed-effect
formal tests for funnel plot asymmetry where relevant. For con- versus random-effects analyses for outcomes with substantial sta-
tinuous outcomes we used the test proposed by Egger 1997, and tistical heterogeneity. Where this was the case relevant comments
for dichotomous outcomes we used the test proposed by Harbord are made in the body of the text.
2006. If asymmetry was detected in any of these tests or was sug-
gested by a visual assessment, we performed exploratory analyses
to investigate it.
Data synthesis RESULTS

We carried out statistical analysis using the Review Manager soft-
ware (RevMan 2011).
We used fixed-effect meta-analysis for combining data where it
was reasonable to assume that studies were estimating the same
Description of studies
underlying treatment effect: i.e. where trials were examining the See: Characteristics of included studies; Characteristics of excluded
same intervention, and the trials’ populations and methods were studies; Characteristics of studies awaiting classification.
judged sufficiently similar. If there was clinical heterogeneity suf- Twenty-seven trials, involving 3274 labouring women, met our
ficient to expect that the underlying treatment effects differed be- criteria for inclusion.
tween trials, or if substantial statistical heterogeneity was detected, (a) Cochrane Pregnancy and Childbirth Group’s Trials Register
we used random-effects meta-analysis to produce an overall sum- (September 2011). From the references identified, 54 trials met
mary if an average treatment effect across trials was considered the criteria for assessment and 27 were included.
clinically meaningful. We treated the random-effects summary as (b) Manual search: three received, all meeting criteria for assess-
the average range of possible treatment effects and we discussed ment, one added as additional reference to study already included.
the clinical implications of treatment effects differing between tri- (c) Manual search from reference list in assessed studies: three
als. If the average treatment effect was not clinically meaningful studies assessed, none included.
we did not combine trials. (d) Personal communications: ongoing.

Results of the search 1998; Patel 2003a) the study period involved only the initial in-
Twenty-seven trials, involving 3274 women, were included. We trathecal or epidural bolus with assessments and data collection
excluded 27 studies. For details of the individual included and ex- stopping at the time of request for “top-up” analgesia. In the re-
cluded studies, see the tables of Characteristics of included studies maining studies there was a varied assortment of regimens for
and Characteristics of excluded studies. epidural maintenance based around timing of commencement rel-
ative to initial injection as well as mode of epidural delivery and the
types of solutions used. Local anaesthetic boluses of bupivacaine
Included studies 0.125% or 0.25% for rescue analgesia were specified in a num-
ber of studies (Abouleish 1991; Abrao 2009; Cohen 2006; Cortes
2007; Dunn 1998; Gomez 2001; Goodman 2006; Hepner 2000;
Methods and techniques Ngamprasertwong 2007; Price 1998; Roux 1999; Skupski 2009;
Thomas 2005; Tsen 1999; Vernis 2004), while in others this was
All included studies reported obtaining informed consent from the
left up to the discretion of the attending anaesthetist (COMET
participants after prior ethics committee approval. In one study,
2001a; Nickells 2000; Van de Velde 1999). No specific statement
verbal rather than written consent was obtained (Nickells 2000),
was made regarding criteria for intervention in the event of in-
the explanation being that the techniques being compared were
adequate analgesia in the remaining eight studies (Breen 1999;
already in routine use. There was no indication as to the form of
Caldwell 1994; Kartawiadi 1996; Medina 1994; Parry 1998; Patel
the consent in five other studies (Cohen 2006; Goodman 2006;
2003a; Sezer 2007; Zeidan 2004).
Medina 1994; Patel 2003a; Thomas 2005).
Eighteen studies mentioned a fluid preload with crystalloid before
the insertion of epidural or combined spinal-epidural (CSE); the
volumes were either not stated (Medina 1994; Ngamprasertwong Participants
2007) or highly varied: 500 mL (COMET 2001a; Gomez 2001;
Price 1998; Roux 1999; Vernis 2004), 500 to 1000 mL (Breen All the included trials studied healthy women in labour requesting
1999; Parry 1998), or at least 1000 mL (Skupski 2009; Tsen 1999; regional analgesia. Most stipulated a singleton, obstetrically un-
Zeidan 2004). Four studies related the fluid bolus to parturient complicated pregnancy at term, as with Ngamprasertwong 2007
weight, giving 10 mL/kg (Abrao 2009; Bhagwat 2008; Cortes and Skupski 2009. Nineteen studies specifically defined the stage
2007) or 15 mL/kg over 15 minutes (Van de Velde 1999). of labour by stating the degree of cervical dilatation as an upper
Almost all studies described a single space, needle-through-needle limit for inclusion or as an exclusion. In these studies, the accept-
technique for CSE; six studies gave no indication (Abrao 2009; able dilatation of the cervix ranged to an upper limit of 4 cm or
Cohen 2006; Cortes 2007; Goodman 2006; Patel 2003a; Skupski less (Goodman 2006; Roux 1999; Tsen 1999; Zeidan 2004) or up
2009). Where stated, patient position was relatively evenly divided to 5 cm (Bhagwat 2008; Breen 1999; Cortes 2007; Dunn 1998;
between the sitting (Dunn 1998; Gomez 2001; Hepner 2000; Gomez 2001; Hepner 2000; Kartawiadi 1996; Medina 1994; Price
Nickells 2000; Parry 1998; Roux 1999; Sezer 2007; Thomas 2005; 1998; Sezer 2007; Thomas 2005), 6 cm (Abrao 2009; Sezer 2007;
Vernis 2004) and lateral (Bhagwat 2008; Kartawiadi 1996; Medina Vernis 2004) or 7 cm (Van de Velde 1999). Of the other eight
1994; Ngamprasertwong 2007; Price 1998; Tsen 1999; Van de included studies that did not specifically state a degree of cervi-
Velde 1999; Zeidan 2004) alternatives. One study allowed either cal dilatation there were less specific or indirect means of deter-
sitting or lateral position for insertion (COMET 2001a) and in the mining the stage of labour. Thus ’first stage of labour’ was one
remaining nine studies (Abouleish 1991; Abrao 2009; Breen 1999; inclusion (Parry 1998) and ’imminent delivery’ was another spe-
Caldwell 1994; Cohen 2006; Cortes 2007; Goodman 2006; Patel cific exclusion (COMET 2001a). Exclusion criteria varied greatly
2003a; Skupski 2009) there is no detail of patient position. Only with nine included studies not stating any explicit criteria prevent-
one study (Skupski 2009) specifically commented on maternal ing participation (Abouleish 1991; Caldwell 1994; Cohen 2006;
position during labour or ongoing intravenous fluid therapy, both Cortes 2007; Medina 1994; Patel 2003a; Nickells 2000; Sezer
of which could conceivably have had an effect on maternal and 2007; Thomas 2005). Only three of the included studies (Gomez
fetal parameters subsequently measured. Operators in the included 2001; Sezer 2007; Tsen 1999) stipulated spontaneous onset of
studies were not blinded to the technique although in all studies labour as an entry criterion and no study excluded women on
the assessor was reported as being blinded to group allocation for at the basis of need for labour augmentation. Eight included stud-
least some of the outcome assessments. One further study (Gomez ies (Abouleish 1991; Breen 1999; COMET 2001a; Dunn 1998;
2001) was described as single-blinded but this was not further Kartawiadi 1996; Parry 1998; Vernis 2004; Zeidan 2004) spec-
defined. ified previous opioid administration over a range of one to four
In all of the included studies a CSE technique was compared with hours as a criterion for exclusion and in two further studies (Abrao
epidural analgesia in the first stage of labour. In five of the in- 2009; Van de Velde 1999) women were excluded if they had re-
cluded papers (Breen 1999; Dunn 1998; Nickells 2000; Parry ceived “sedative or analgesic drugs”.

Interventions epidural group (Caldwell 1994; Cortes 2007; Ngamprasertwong
2007; Roux 1999; Thomas 2005) or using less (COMET 2001a;
There was considerable heterogeneity between trials with respect
Gomez 2001; Tsen 1999). Four studies (Caldwell 1994; Gomez
to the drug combinations used, both intrathecally and epidurally,
2001; Ngamprasertwong 2007; Tsen 1999) involved the use of a
the timing of subsequent dosing after initial analgesia and the
low-dose infusion down the epidural catheter for maintenance. In
method of epidural drug delivery. In the context of categorising the
these studies the infusions were started immediately after the ini-
epidural drug dose/concentration used, the term traditional was
tial bolus in the epidural groups. In three other studies (COMET
used for trials where the epidural local anaesthetic (LA) concen-
2001a; Cortes 2007; Roux 1999) maintenance was with inter-
tration was the equivalent of bupivacaine 0.25% or more; lower
mittent epidural boluses at patient request. COMET 2001a used
concentrations were defined as low-dose. In the CSE groups, there
0.25% bupivacaine in the epidural group but bupivacaine 0.15%
were three types of interventions; LA plus opioid, opioid alone or
plus fentanyl 2 µg/mL in the CSE group; both Cortes 2007 and
null CSE where there was a dural puncture with no intrathecal
Roux 1999 used 0.25% bupivacaine in both. In the remaining trial
injection of drugs. Using these definitions the comparisons fell
(Thomas 2005) in which no intrathecal drugs were injected as part
into six categories as detailed below:
of the CSE technique, all women received the same epidural man-
1. LA plus opioid CSE versus traditional epidural - three
agement. This was also the only trial in this category which em-
studies, 846 women (COMET 2001a; Gomez 2001; Tsen 1999);
ployed a patient-controlled epidural analgesia (PCEA) technique
2. LA plus opioid CSE versus low-dose epidural - 18 studies,
for maintenance of analgesia. This involved bupivacaine 0.11%
2086 women (Abrao 2009; Bhagwat 2008; Cohen 2006;
plus fentanyl 2 µg/mL at 10 mL/hour with 5 mL bolus and lock-
COMET 2001a; Goodman 2006; Hepner 2000; Kartawiadi
out of 10 minutes.
1996; Medina 1994; Nickells 2000; Parry 1998; Patel 2003a;
There were 16 included studies that employed a low-dose LA
Price 1998; Skupski 2009; Van de Velde 1999; Vernis 2004;
epidural group compared with CSE. In these trials there was a
Zeidan 2004);
range of techniques used to establish the epidural block in the
3. opioid only CSE versus traditional epidural - four studies,
epidural groups. All employed bupivacaine as the local anaesthetic
229 women (Caldwell 1994; Cortes 2007; Ngamprasertwong
in concentrations from 0.0625% to 0.125% and in combination
2007; Roux 1999);
with fentanyl (20 to 75 µg) or sufentanil (5 to 10 µg) to a to-
4. opioid only CSE versus low-dose epidural - two studies,
tal volume of between 10 and 20 mL. Seven trials (Abouleish
102 women (Abouleish 1991; Sezer 2007);
1991; Abrao 2009; Goodman 2006; Kartawiadi 1996; Medina
5. opioid only CSE versus test LA/opioid epidural - two
1994; Van de Velde 1999; Vernis 2004) used bupivacaine 0.125%
studies, 111 women (Breen 1999; Dunn 1998);
with added fentanyl or sufentanil. Eight further studies used even
6. null CSE versus traditional epidural - one study, 251
lower concentrations with bupivacaine 0.1% (Nickells 2000; Parry
women (Thomas 2005).
1998; Price 1998) and 0.0625% (Bhagwat 2008; Hepner 2000;
There were eight trials that included a traditional epidural group
Skupski 2009; Zeidan 2004) and in Cohen 2006 0.04% ropiva-
(Caldwell 1994; COMET 2001a; Cortes 2007; Gomez 2001;
caine plus sufentanil was used. In relation to the CSE groups, in all
Ngamprasertwong 2007; Roux 1999; Thomas 2005; Tsen 1999).
except one trial (Abouleish 1991), the initial intrathecal injection
One of these studies (COMET 2001a) involved comparisons of a
consisted of LA plus opioid using bupivacaine and either sufen-
CSE group with both traditional and a low-dose epidural group (see
tanil or fentanyl. In the Abouleish 1991 trial the CSE group con-
below) and so contributed an additional 704 women to category
sisted of intrathecal morphine 0.2 mg alone and in Cohen 2006,
(1) above and 701 women to category (2). With the exception of
5 µg of sufentanil and 2 mg of ropivacaine was used. For the other
one study (Thomas 2005), all studies fulfilling this criterion used
studies the doses employed ranged from 1.25 to 3.75 mg bupiva-
0.25% bupivacaine boluses at some time, with volumes ranging
caine, 5 to 25 µg fentanyl and 1.5 to 5 µg sufentanil. A common
from 6 to 12 mL; Thomas 2005 used 2% lignocaine to a total vol-
technique used in six studies was that of bupivacaine 2.5 mg plus
ume of 10 mL. In the three trials with a LA plus opioid group, the
fentanyl 25 µg. In three studies (Nickells 2000; Parry 1998; Patel
CSE technique involved an intrathecal injection of bupivacaine
2003a) there was no maintenance analgesia stated. In two of the
2.5 mg in combination with either fentanyl (COMET 2001a;
remaining studies intermittent boluses of either 0.1% (Nickells
Gomez 2001) or sufentanil (Tsen 1999). Of the four trials with
2000) or 0.125% (Kartawiadi 1996) bupivacaine were delivered
an opioid only CSE group, Caldwell 1994 used a combination of
down the indwelling epidural catheter for maintenance after re-
fentanyl 25 µg plus morphine 0.25 mg intrathecally, while Roux
turn of pain. Six studies (Goodman 2006; Hepner 2000; Medina
1999 used sufentanil 10 µg; the other two trials (Cortes 2007;
1994; Ngamprasertwong 2007; Skupski 2009; Zeidan 2004) used
Ngamprasertwong 2007) used 25 µg of fentanyl only. Whilst the
low-dose LA plus opioid bolus then infusion for maintenance after
techniques of drug dosing varied between studies, it was noted
return of pain in both groups. In Hepner 2000 the first additional
in these trials that there were essentially two approaches to sub-
analgesia was provided by a bolus of 0.0625% bupivacaine with
sequent epidural management in the CSE groups, either using
added fentanyl, bicarbonate and epinephrine. Zeidan 2004 used
effectively the same total epidural drug administration as in the

0.0625% bupivacaine plus fentanyl 1.5 µg/mL and Medina 1994 additional analgesic intervention. Only two studies (Parry 1998;
used 0.125% bupivacaine plus sufentanil 0.5 µg/mL. In Goodman Patel 2003a) did not quote any data regarding the effectiveness of
2006, Ngamprasertwong 2007 and Skupski 2009 both groups pain relief but had primary outcomes related to effects on the baby
had infusion of bupivacaine 0.0625% plus fentanyl 2 µg/mL at 12 and epidural/CSE effects on dorsal column function respectively.
mL/hr.The low-dose epidural infusion group in COMET 2001a All but 10 studies (Abouleish 1991; Abrao 2009; Bhagwat 2008;
had analgesia established with a bolus of 0.1% bupivacaine with Caldwell 1994; Goodman 2006; Medina 1994; Patel 2003a; Roux
fentanyl and an immediate infusion of the same solution for main- 1999; Skupski 2009; Thomas 2005) quoted figures for degree of
tenance. Data from this group were independently compared with motor blockade, but only data from papers quoting numbers of
the traditional epidural group. Five studies used a PCEA technique women who actually walked during labour were used in the anal-
for maintenance of analgesia. One (Van de Velde 1999) used bo- ysis of ability to mobilise (Breen 1999; Cohen 2006; COMET
luses of 4 mL 0.125% bupivacaine with sufentanil 0.75 µg/mL and 2001a; Dunn 1998; Parry 1998; Price 1998; Zeidan 2004). In
epinephrine 1.25 µg/mL and a lockout time of 15 minutes. The one trial (Collis 1995) only women receiving the CSE technique
second (Price 1998) used 10 mL 0.1% bupivacaine with added were assessed for motor block and if able to straight-leg-raise satis-
fentanyl 2 µg/mL delivered with a lockout time of 30 minutes. factorily, they were encouraged to mobilise. However, the women
Vernis 2004 used bupivacaine 0.125% plus sufentanil 0.25 µg/mL receiving the traditional epidural analgesia were not assessed and
with a 4 mL bolus and 10 minute lockout. Sezer 2007 used PCEA not encouraged to walk. One other study (Nageotte 1997) in-
with 5 mL bolus of bupivacaine 0.1% plus fentanyl 2 µg/mL with volved two CSE groups, identical in all other respects except that
a 10 minutes lockout. Bhagwat 2008 used bupivacaine 0.0625% the women in one group were actively encouraged to walk while
plus fentanyl 2 µg/mL at a rate of 8 to 12 mL/hr to maintain T10 those in the second CSE group were discouraged from mobilising.
block via PCEA pump. In Abrao 2009 different concentrations No data on mobility were presented for the women in the epidu-
of bupivacaine were given based on cervical dilation upon patient ral group. As there was an actively promoted difference in treat-
request. ment between epidural and CSE groups in both studies, this cast
In two studies the main epidural bolus consisted of opioid alone, doubt on the maintenance of blinding, suggesting the possibility
either fentanyl 100 µg (Breen 1999) or sufentanil 4 µg (Dunn of performance bias and a loss of the benefit of randomisation.
1998). In each case the opioid bolus was only administered after Sensitivity analysis was performed and both studies (Collis 1995;
a test dose of 3 mL lignocaine 1.5%. The intrathecal component Nageotte 1997) were excluded. Similarly in COMET 2001a only
of the CSE in both trials was sufentanil 10 µg; there was no stated women in the low-dose infusion and CSE groups were allowed
analgesia maintenance in either study. to mobilise, with no data from the traditional epidural group for
comparison. In Cohen 2006 and Cortes 2007 all women in both
Maternal outcomes
groups were able to mobilise.
The incidence of short-term side effects and complications, along
No study reported time taken from request of maternal analgesia
with maternal and neonatal effects was also presented in most
to the time the mother felt the level of pain relief was satisfactory.
studies. Maternal satisfaction with analgesia was the primary out-
However, one study (Hepner 2000) commented on the need to
come for one excluded study (Collis 1995) but measurement of
take into account the additional time required to prepare certain
satisfaction postdelivery featured as a secondary outcome in seven
solutions and the impact this may have on the time from patient
of the included trials (Gomez 2001; Hepner 2000; Kartawiadi
request to establishing analgesia. We also evaluated onset of pain
1996; Price 1998; Van de Velde 1999; Vernis 2004; Zeidan 2004).
relief from time of initial injection, acknowledging that this result
Typically, the assessment of satisfaction was very simple. For ex-
comes more from the practical realities of conducting a research
ample, Vernis 2004 used a four-point Likert scale response to the
trial rather than what may be of interest to consumers. The stated
written question, ’Were you satisfied with your labour?’. Gomez
primary outcome of 18 of the included studies was related to the
2001 presented satisfaction data as visual analogue scale scores
quality of analgesia and data on analgesic efficacy were presented as
at time of delivery but these could not be included in the data
a secondary outcome in a further eight trials (Bhagwat 2008; Breen
tables. Incidence of headache in the days following delivery was
1999; COMET 2001a; Gomez 2001; Hepner 2000; Skupski
quoted widely, and the use of blood patch for post dural punc-
2009; Tsen 1999; Zeidan 2004). These data took the form of visual
ture headache was analysed from eight studies (Abouleish 1991;
analogue scores in most cases (Abouleish 1991; Breen 1999; Dunn
Dunn 1998; Hepner 2000; Kartawiadi 1996; Price 1998; Roux
1998; Gomez 2001; Hepner 2000; Kartawiadi 1996; Medina
1999; Vernis 2004; Zeidan 2004). One study quoted dural tap rate
1994; Price 1998; Roux 1999; Tsen 1999; Van de Velde 1999;
but not rate of headache or blood patch requirement (COMET
Vernis 2004; Zeidan 2004) and in one study was retrospectively
2001a). One excluded study (Finegold 2003) investigated uterine
assessed by a postnatal interview (COMET 2001a). Eleven studies
contraction rates and endogenous oxytocin levels as primary out-
(Abouleish 1991; COMET 2001a; Dunn 1998; Gomez 2001;
comes but these were not included in our measures.
Hepner 2000; Medina 1994; Nickells 2000; Price 1998; Thomas
The effect on the progress of labour was the main outcome in
2005; Vernis 2004; Zeidan 2004) detailed the requirement for

four studies, two assessing the rate of cervical dilatation (Bhagwat gar score and found no difference between groups (Abrao 2009;
2008; Tsen 1999) and two focusing on mode of delivery (COMET Bhagwat 2008; Cohen 2006; Sezer 2007).
2001a; Zeidan 2004). Other side effects analysed included the oc-
currence of hypotension, respiratory depression, pruritus, nausea
Excluded studies
and vomiting, urinary retention and sedation. Data concerning
longer-term outcomes were presented in only one (Medina 1994) Twenty seven studies were excluded. Reasons for exclusion fell
of the trials although another (COMET 2001a) explicitly referred into three broad categories. Nine studies (Camann 1992; Camann
to the collection of such data not yet completed. Of note, no study 1998; Collis 1994; Collis 1999a; Collis 1999b; D’Angelo 1994;
looked at the economics and use of resources involved in the pro- Harsten 1997; Pham 1996; Rosenfeld 1998; Van de Velde 2004)
vision of both analgesic regimens, such as comparative cost of con- consisted of study designs in which all women received a spinal
sumables, duration and cost of stay in hospital, or need for read- injection or dural puncture plus epidural and as such were not
mission or follow-up after discharge. The effect on the progress of specifically comparing a combined spinal epidural with epidural
labour was the main outcome in four studies, three assessing the alone. Six other studies (Cascio 1996; Cooper 2010; Groves 1995;
rate of cervical dilatation (Bhagwat 2008; Sezer 2007; Tsen 1999) Kassapidis 1997; Patel 2003b; Stocche 2001), although comparing
and one focusing on mode of delivery (COMET 2001a). CSE with epidurals for labour analgesia, reported outcomes that
were not part of our analysis. A further 12 studies (Backus 1996;
Collis 1995; Dresner 1999; Finegold 2003; Fogel 1999; Leighton
Neonatal outcomes 1996; Nageotte 1997; Nielson 1996; Norris 1994; Norris 2001;
Pan 1996; Pinto 2000) exhibited a variety of methodological and
Neonatal assessment was carried out in all but six studies (Breen study design issues. For example, Leighton 1996, Nielson 1996,
1999; Gomez 2001; Goodman 2006; Nickells 2000; Price 1998; Norris 1994 and Norris 2001 were not randomised studies. Also,
Tsen 1999). In all other studies, Apgar scores were used as an out- Backus 1996 and Fogel 1999 had significant treatment differences
come measure. In Dunn 1998 and Ngamprasertwong 2007 neona- within groups, while in Collis 1995 and Nageotte 1997 there
tal Apgar scores were stated as not differing between groups but no were significant differences in the management of patients between
actual numbers were quoted. In the remaining eight included stud- groups which are likely to have directly influenced outcomes, no-
ies, four quoted numbers of neonates with Apgar scores of less than tably mobilisation.
seven at five minutes, while four others gave data on those scor-
ing less than eight (Abouleish 1991; COMET 2001a; Kartawiadi
1996; Parry 1998). In addition, five studies included cord blood
gas analysis (Abouleish 1991; Abrao 2009; Caldwell 1994; Hepner
Risk of bias in included studies
2000; Van de Velde 1999). These data were presented as mean There was a wide range of methodological quality. Details are
pH +/- SD, rather than the number of neonates demonstrating a shown in the table of Characteristics of included studies. Of the
predefined degree of acidosis. Only one study (COMET 2001a) 27 included studies, only four (Breen 1999; Goodman 2006;
included data on the number of neonates requiring admission to a Hepner 2000; Kartawiadi 1996) were fully consistent with the
special care neonatal unit. Two studies looked at fetal bradycardia methodological principles defined in the Cochrane Handbook for
as primary outcome (Abrao 2009; Skupski 2009). In the study by Systematic Reviews of Interventions (Higgins 2011).
Bhagwat 2008, there was one stillbirth with cord around the neck See Figure 1 and Figure 2 for summary of ’Risk of bias’ assessments
in the CSE group noted. Four other studies included mean Ap- for all studies.

Figure 1. ’Risk of bias’ graph: review authors’ judgements about each risk of bias item presented as
percentages across all included studies.

Figure 2. ’Risk of bias’ summary: review authors’ judgements about each risk of bias item for each included
study.

Allocation
2005; Tsen 1999; Van de Velde 1999; Vernis 2004; Zeidan 2004)
All included studies stated that women were randomly allocated as all expected outcomes were reported. We assessed the remaining
to treatment groups. Whilst a range of methods for randomisation two studies as being at unclear risk of bias: in one study primary
and concealment of allocation were stated, we assessed 11 stud- and secondary outcomes were not stated (Medina 1994); and in
ies as being at low risk of bias for randomisation (Abrao 2009; the other study reporting of detail of outcomes was unclear (Patel
Bhagwat 2008; Breen 1999; Caldwell 1994; COMET 2001a; 2003a).
Goodman 2006; Hepner 2000; Kartawiadi 1996; Skupski 2009;
Thomas 2005; Zeidan 2004) and 14 studies as being at low risk
of bias for allocation concealment (Abrao 2009; Breen 1999; Other potential sources of bias
Caldwell 1994; COMET 2001a; Goodman 2006; Hepner 2000; No other sources of bias were identified in 23 of the included
Kartawiadi 1996; Ngamprasertwong 2007; Nickells 2000; Price studies (Abouleish 1991; Abrao 2009; Bhagwat 2008; Breen
1998; Sezer 2007; Skupski 2009; Tsen 1999; Vernis 2004). Meth- 1999; Caldwell 1994; Cohen 2006; COMET 2001a; Cortes
ods employed included computer randomisation and numbered, 2007; Dunn 1998; Gomez 2001; Goodman 2006; Hepner
sealed, opaque envelopes (Caldwell 1994), random-number tables 2000; Kartawiadi 1996; Medina 1994; Ngamprasertwong 2007;
with sealed envelopes (Hepner 2000) and computerised allocation Nickells 2000; Parry 1998; Patel 2003a; Price 1998; Roux 1999;
provided by external sources (COMET 2001a). In the remaining Sezer 2007; Skupski 2009; Thomas 2005; Tsen 1999; Van de
studies, the methods of randomisation and allocation concealment Velde 1999; Vernis 2004; Zeidan 2004). In the other four stud-
used were not clearly described. ies, we assessed other risk of bias as being unclear (Bhagwat 2008;
Nickells 2000; Skupski 2009; Vernis 2004): one study (Bhagwat
2008) had not dealt with one still birth in the CSE group (cord
Blinding
around neck); one study (Nickells 2000) was stopped after three
We assessed 15 studies as being at low risk of bias for perfor- months and so there were slightly uneven group sizes; one study
mance and detection bias (Abouleish 1991; Abrao 2009; Bhagwat (Skupski 2009) was underpowered to detect the difference in fetal
2008; Breen 1999; Dunn 1998; Goodman 2006; Hepner 2000; heart rate changes; and one study (Vernis 2004) was stopped early.
Kartawiadi 1996; Nickells 2000; Parry 1998; Price 1998; Roux
1999; Thomas 2005; Tsen 1999; Van de Velde 1999); in nine stud-
Effects of interventions
ies risk of bias was unclear (Caldwell 1994; Cohen 2006; Cortes
2007; Gomez 2001; Medina 1994; Patel 2003a; Sezer 2007; Vernis Twenty-seven trials, involving 3274 labouring women, met our
2004; Zeidan 2004); and we assessed three studies as being at high criteria for inclusion.
risk of bias (COMET 2001a; Ngamprasertwong 2007; Skupski We performed analyses on all included studies against 26 out-
2009). comes. This was performed as two separate sets of comparisons.
The first set involved all combined spinal-epidural (CSE) variants
versus traditional epidurals and the second set was all CSE forms
Incomplete outcome data versus low-dose epidurals and variants. For a summary of analyses
This was an issue for two studies (Abrao 2009; Nickells 2000). see Data and analyses.
In Abrao 2009, of those originally randomised, 15% were not
analysed; for neonatal pH this was 29%. In Nickells 2000, unclear
data tables prevented us from using some of their reported data CSE versus traditional epidural
for analysis and it was not clear whether 18 analgesic failures (nine Of the CSE versus traditional epidural analyses four outcomes
in each group) were included in the analysis of their results. In all showed a significant difference. The time from first injection to
the remaining studies, complete outcome data were available. effective analgesia was less with CSE (mean difference (MD) -
2.87 minutes; 95% confidence interval (CI) -5.07 to -0.67; 129
women (Analysis 1.1)) based on two studies (Ngamprasertwong
Selective reporting 2007; Roux 1999). There was a reduced need for rescue analge-
We assessed 25 studies as being at low risk of bias for selective sia for CSE based on one study (Gomez 2001) with a risk ratio
reporting (Abouleish 1991; Abrao 2009; Bhagwat 2008; Breen (RR) of 0.31 (95% CI 0.14 to 0.70; 42 women (Analysis 1.3)).
1999; Caldwell 1994; Cohen 2006; COMET 2001a; Cortes CSE was also more favourable with respect to the need for in-
2007; Dunn 1998; Gomez 2001; Goodman 2006; Hepner 2000; strumental delivery with RR 0.81 (95% CI 0.67 to 0.97; 1015
Kartawiadi 1996; Ngamprasertwong 2007; Nickells 2000; Parry women (Analysis 1.19)) based on six studies (COMET 2001a;
1998; Price 1998; Roux 1999; Sezer 2007; Skupski 2009; Thomas Cortes 2007; Gomez 2001; Ngamprasertwong 2007; Roux 1999;

Tsen 1999). CSE was also associated with less urinary retention studies. However, as has been remarked upon in previous versions
based on the COMET 2001a study (RR 0.86; 95% CI 0.79 to of this review, no study reported our primary outcome of interest
0.95; one study, 704 women (Analysis 1.10)). CSE was associ- with regards to time of onset of pain relief in labour from the time
ated with a slightly lower umbilical venous pH in comparison to of patient request.
the epidural group, although this result was based on only one For the analyses of CSE versus low-dose epidurals, CSE was as-
study involving morphine and fentanyl for the initial intrathecal sociated with more pruritus (average RR 1.80; 95% CI 1.22 to
injection (Caldwell 1994), and statistical significance was border- 2.65; 11 studies, 959 women; random-effects, T² = 0.26, I² =
line (MD -0.03; 95% CI -0.06 to -0.00; one study, 55 women 84% (Analysis 2.9)). There was substantial heterogeneity between
(Analysis 1.22)). studies reflecting once again the marked variability in definitions
No differences between CSE and epidural were seen for the num- used.
ber of women who mobilised, post dural puncture headache, pru- There were no significant differences between CSE and low-dose
ritis, nausea and vomiting, hypotension or the rate of caesarean epidural with regard to modes of delivery and the need for labour
birth. Also, there were no significant differences for the following augmentation. There was also no significant difference between
neonatal outcomes: umbilical arterial pH, Apgar score less than CSE and low-dose epidurals with respect to the maternal side ef-
seven or less than eight at five minutes and the number of admis- fects of urinary retention, nausea and vomiting, post dural punc-
sions to the neonatal unit. ture headache, known dural tap and need for a blood patch, or for
Due to results not being statistically significant or outcomes re- the need of rescue analgesia. Maternal satisfaction with analgesia
ported with zero data, it was not possible to draw any conclusions was also not significantly different based on seven studies (520
with respect to the following outcomes: number of women with women) (see Analysis 2.4). However, there was substantial hetero-
effective analgesia in the first 10 minutes after injection, number geneity in this result and this probably reflects the wide variation
of women satisfied with analgesia, number of women requiring a in and perhaps simplistic methods generally used for assessing this
blood patch, maternal respiratory depression and umbilical cord important outcome.
pH. In relation to all of the neonatal outcomes there was also no differ-
ence with umbilical venous pH, umbilical cord pH, Apgar scores
at five minutes and the number of neonates requiring neonatal
Subgroup analyses unit admission. It was not possible to draw any conclusions with
No subgroup differences between opioid CSE and CSE were ob- respect to the following outcomes: maternal respiratory depression
served: known dural tap (Analysis 1.7); pruritus (Analysis 1.9); and maternal sedation. No women experienced maternal respira-
nausea/vomiting (Analysis 1.11); hypotension (Analysis 1.12); tory depression in the studies that reported on this outcome and
labour augmentation required (Analysis 1.16); normal delivery maternal sedation was not a reported outcome in the included
(Analysis 1.18); instrumental delivery (Analysis 1.19) or caesarean studies. Two other outcomes are worth highlighting specifically.
section (Analysis 1.20). Firstly, mobilisation in labour was reported by seven studies (in-
volving 1200 participants) and there was no difference between
the techniques. Secondly, the occurrence of hypotension exhibited
CSE versus low-dose epidural substantial heterogeneity, again as a result of the diverse range of
For the analyses of CSE versus low-dose epidurals and variants definitions used. We have reported this outcome as not significant.
there were three outcomes which were statistically significant. Both However we conducted both subgroup and sensitivity analyses as a
measures of speed of onset of analgesia from the time of injection result of the wide variation of results seen between different studies
indicated a faster onset for CSE versus low-dose epidural. The and a funnel plot looking for any effects of small studies (Figure 3).
mean time of onset of effective analgesia was -5.42 minutes (95% The small number of subjects in the different subgroups resulted
CI -7.26 to -3.59; five studies, 461 women; random-effects,T² = in there being no discernible effect. However, within the local
3.27, I² = 77% (Analysis 2.1)), while the risk ratio of effective anaesthetic plus opioid CSE versus low-dose epidural comparison
analgesia at 10 minutes was 1.94 in favour of CSE (95% CI 1.49 to there appears to be a trend to there being a more favourable out-
2.54) based on a single study with 101 women (Analysis 2.2). Time come for epidural over CSE; a fixed-effect analysis would produce
of onset of effective analgesia showed substantial heterogeneity, but a significant result.
this would be expected given the variation in techniques between

Figure 3. Funnel plot of comparison: 2 Combined spinal-epidural versus low-dose epidural, outcome: 2.12
Hypotension.
2.8); urinary retention (Analysis 2.10); nausea/vomiting (Analysis

Adverse events
2.11); hypotension (Analysis 2.12); labour augmentation required
We included the incidence of longer-term sequelae (e.g. neurolog- (Analysis 2.16); normal delivery (Analysis 2.18); instrumental de-
ical) as an outcome measure as this has been raised as a source of livery (Analysis 2.19); caesarean section (Analysis 2.20); umbilical
concern in the past regarding the routine use of CSE analgesia for arterial pH (Analysis 2.21); umbilical venous pH (Analysis 2.22)
labour. In Medina 1994, in the CSE group there was one case of or Apgar score less than seven at five minutes (Analysis 2.24).
reflex sympathetic pain of the foot which required two paraverte- However, subgroup differences were observed for the following
bral blocks to resolve. In another study (Vernis 2004) there was two outcomes: number of women who mobilise (P = 0.04, I² =
one woman in the CSE group who developed meningitis which 76.5%; Analysis 2.5) and pruritus (P = 0.03, I² = 79.4%; Analysis
responded effectively to intravenous antibiotics. COMET 2001a 2.9).
made reference to the ongoing collection of data not yet com-
pleted.
DISCUSSION
Subgroup analyses There is no standard combined spinal-epidural (CSE) or epidural
No subgroup differences between opioid CSE, null CSE and CSE technique and this necessitated categorising individual interven-
were observed for the following outcomes: time from first injections into groups for analysis, and the use of multiple comparisons
tion to effective analgesia (Analysis 2.1); need for rescue anal- for individual outcomes. See additional tables, Table 1 and Table
gesia (Analysis 2.3); number of women satisfied with analgesia 2, for details. Nonetheless, in an attempt to maintain relevance
(Analysis 2.4); number of women who mobilise (Analysis 2.5); with evolving clinical practice, we performed comparisons sepa-
post dural puncture headache (Analysis 2.6); known dural tap rately for CSE versus traditional epidurals and for low-dose epidu-
(Analysis 2.7); number of women requiring blood patch (Analysis rals. This appears to have some clinical relevance supported by

this review with there being several outcomes significantly favour- women participated in all 27 included studies combined. This is
ing CSE over the traditional forms which was not apparent when insufficient to assess the occurrence of very rare events. However,
CSE was compared with the lower-dose variants, notably higher the inclusion of data on long-term outcomes should still form part
urinary retention, higher instrumental delivery rate and the need of large trials, such as COMET 2001a, so that perhaps in the fu-
for rescue analgesia with traditional epidurals. ture some benefit may be gained by collating the evidence from
large numbers of studies. In the meantime, clinicians will have
Proposed benefits of CSE analgesia in labour over epidural pain to rely on other forms of evidence, such as case reports and large
relief are increased mobility and a postulated beneficial effect on cohort studies, for information on such rare events as meningitis
mode of delivery. In this update there are now data from eight stud- and other neurological complications.
ies involving 1240 women including one study involving tradi-
tional epidurals (Cortes 2007; 40 women) and seven studies (1200
women) involving low-dose epidurals (Breen 1999; Cohen 2006;
COMET 2001a; Dunn 1998; Parry 1998; Price 1998; Zeidan AUTHORS’ CONCLUSIONS
2004). There was no difference seen in the number of women who
Implications for practice
actually mobilised. In relation to mode of delivery there is also no Both combined spinal-epidural and epidural techniques are shown
apparent benefit attributable to CSE other than for a lower instru- to provide effective pain relief in labour. There appears to be little
mental rate when compared with traditional epidurals. The rate basis for offering one technique over the other, with no difference
of caesarean section would appear to be influenced by factors that in overall maternal satisfaction despite a slightly faster onset with
to date have not emerged against these modes of regional anal- combined spinal-epidural (CSE) and less pruritus with low-dose
gesia. This is of interest not only in regard to progress of labour epidurals. There is no difference in ability to mobilise, obstetric
but also in relation to concerns for unfavourable fetal heart rate outcome or neonatal outcome. The significantly higher incidence
changes that have been attributed to the use of CSE techniques. with traditional epidural techniques of urinary retention based on
This review does not include any outcomes specifically linked to one study involving 703 women and of rescue interventions, also
fetal heart rate. However, if these effects are real there appears to be with one other study involving 42 women, would favour the use
no support from this review of a significant translation of concern of low-dose epidurals, although this should be tempered by the
for the fetus to an increased rate of caesarean delivery. In relation knowledge that only single studies have been involved in both
to neonatal outcome there was no difference between CSE and instances.
epidural as identified by Apgar scores less than eight or seven at
five minutes or the need for neonatal unit admission. Any possible Implications for research
differences between the two techniques in relation to the occur-
Future trials should include as an endpoint the time taken from
rence of unfavourable fetal heart rate changes during labour were
maternal request for pain relief until effective pain relief is estab-
not apparent from these results.
lished. This may be important as the additional tasks involved in
CSE was associated with a higher incidence of pruritus compared the preparation for, and performance of, a combined spinal-epidu-
with low-dose epidural techniques. This is almost certainly a result ral block may potentially offset some of the advantage of quicker
of direct injection of opioids into the subarachnoid space. onset of analgesia. The difference in time of onset from the time
of injection from this review is of the order of one contraction. In
From studies included in this review there was no difference in a busy obstetric service there are many factors that contribute to
the number of women who expressed satisfaction with CSE anal- the total time between a woman requesting pain relief and when
gesia compared with epidural. This was based on seven studies it is actually delivered and these may be far more relevant to the
(involving 520 women), all of which involved low-dose epidurals consumer.
(Bhagwat 2008; Hepner 2000; Kartawiadi 1996; Sezer 2007; Van
de Velde 1999; Vernis 2004; Zeidan 2004). It would appear that While most papers gave data on numbers of women requiring de-
the marginally faster onset from the time of injection, potentially livery by caesarean section, none mentioned the type of anaesthesia
favouring CSE, and the higher incidence of pruritus, presumably for the surgery or the need for conversion to general anaesthesia for
favouring epidurals, do not significantly impact on the overall operative delivery. Avoidance of general anaesthesia still remains
sense of satisfaction. It was noted, however, that the measurement an important goal for obstetric anaesthetists. In this setting there
of satisfaction was typically very simplistic, using four-point scales are pros and cons for both the CSE and epidural techniques. The
of a seemingly global experience. untested epidural catheter of a combined regimen may fail when
topped up for theatre or result in intravascular injection. On the
Randomised controlled trials are not the best means of assessing other hand, there are potential benefits of the intrathecal drugs
differences in the risk of rare complications, such as meningitis, used in terms of providing good surgical conditions and intra-
as they invariably fail to recruit the number of participants neces- operative comfort for the woman. The rate of conversion from
sary to show such differences. In this review a total of over 3200 regional to general anaesthesia is sufficiently common that a very

large study may have sufficient power to provide some answers. Suggested systematic reviews
This could be the basis of a future review if sufficient studies in- A number of studies, both included (Breen 1999; Dunn 1998;
cluded these data. Parry 1998) and excluded from this review (e.g. Camann 1992)
compared an intrathecal injection with an epidural bolus, and
ended the study period with the first request for additional anal-
The collection of data on longer-term sequelae following both gesia. While the exclusion of some such papers was made on other
CSE and epidural pain relief in labour is important. Rare and methodological grounds, the comparison of epidural and intrathe-
long-term adverse effects of spinal and epidural techniques are dif- cal (as opposed to combined spinal-epidural) analgesia for labour
ficult to quantify through small randomised trials such as in this could form the basis of a future review.
review. There are other side effects, however, that can be more Within this review there were a wide range of interventions in-
specifically addressed. Most papers have focused on obstetric out- cluded. Not only did the drugs used differ but also the techniques,
comes. In this review we have also attempted to identify other fac- with studies using repeat boluses or infusions, or both, at different
tors through outcome measures such as respiratory depression and time intervals for the maintenance of analgesia. For the purposes
maternal sedation but very few papers investigated these issues. of this review, all have been included together but with an attempt
Future research work should more specifically address the possible to categorise them into broad groups to assist with interpretation
impact of intrathecal and epidural opioids on both mother and of results. The use of this or a similar structure may facilitate the
baby. One specific area of interest in this regard is a possible link to review of further studies in the future.
breastfeeding success which could be different between CSE and
epidural variants with differing amounts of opioids.
ACKNOWLEDGEMENTS
No reviewed study addressed the economic aspects of both types
of regional pain relief. Future research could include data on such We thank Jane Brown for her contributions to the development of
aspects as cost of consumables, cost and length of hospital stay, the first version of the review; Philippa Middleton, Leanne Jones
consequences of hospital readmission and resources needed for and other members of the Cochrane Pregnancy and Childbirth
patient follow-up after discharge. Group for their valuable feedback.
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on oxytocin and cortisol plasma concentration in labor
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Indicates the major publication for the study

CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]
Abouleish 1991
Methods Randomisation: method not stated “62 women randomly divided into 3 groups”
Blinding: investigators were not blinded to the group allocation. Participant, midwife,
obstetrician and neonatologist were blinded
Criteria for rescue analgesia: if analgesia inadequate after 40 min 10 mL boluses 0.125%
bupivacaine administered until pain relief achieved
Data from all participants used for all outcomes except caesarean section women who
were excluded from analysis re duration and urinary catheterisation
Participants Inclusions: 62 women ASA 1 or 2 at term, with singleton cephalic fetus

Exclusions: none mentioned.
No. lost to follow-up: 0.
NB: 13 women required caesarean section and these women were excluded from the
comparison of urinary retention as they all had an indwelling catheter
Interventions Epidural (n = 22): bolus 10 mL bupivacaine 0.125%. Then as requested further 10 mL

boluses given to maintain analgesia
CSE (n = 20): single space, needle-through-needle (18 G/26 G).
IT injection morphine 0.2 mg, then epidural bolus 10 mL bupivacaine 0.125%. Then
boluses of 10 mL bupivacaine 0.125% as requested
IT morphine group (n = 20): CSE technique as above, but only the IT morphine 0.2
mg given. The epidural catheter only used for additional analgesia on request, when 10
mL bupivacaine 0.125% was given as needed. (This arm was not used in the systematic
review analysis.)
Outcomes VAS pain (0 to 10) every 10 min for 1 hr, then every 20 min. Vital signs monitored at
same time intervals as VAS. SpO2 monitored for 24 hr in all women. Mode of birth
and duration of labour noted. Occurrence of respiratory depression, nausea/vomiting,
pruritus and urinary retention noted. Number with post dural puncture headaches and
treatment required recorded. Neonatal assessment by Apgar scores and cord blood gas
analysis
Notes USA.
Risk of bias
Bias Authors’ judgement Support for judgement
Random sequence generation (selection Unclear risk Stated, “...patients randomly divided”.
bias)
Allocation concealment (selection bias) Unclear risk Investigators were aware of group alloca-
tion.

Abouleish 1991 (Continued)
Blinding (performance bias and detection Low risk Participant, midwife, obstetrician and
bias) neonatologist were blinded
All outcomes
Incomplete outcome data (attrition bias) Low risk Data from all participants used for all
All outcomes outcomes except caesarean section women
who were excluded from analysis re dura-
tion and urinary catheterisation
Selective reporting (reporting bias) Low risk Only with respect to duration and uri-
nary catheterisation for caesarean section
women who were excluded from analysis
Other bias Low risk No other bias evident.
Abrao 2009
Methods Randomisation: a computer-generated random number series.

Allocation concealment: sealed opaque envelopes were generated by a person not related
to the protocol and the anaesthetist received the next in a numbered series
Blinding: participant blinded; outcome assessor and obstetrician blinded to allocation
Criteria for rescue analgesia: not stated.
Statistics were not performed on an intention-to-treat basis; of the 91 participants orig-
inally randomised, 14 were excluded from analysis, 8 in the control group and 6 in
the treatment group (11 failure to maintain adequate CTG recording, 2 proceeding to
vaginal birth in less than 30 minutes, 1 failed spinal); a further 12 did not have umbilical
artery pH data
Participants Inclusions: 77 singleton, cephalic, full term, in active labour with cervical dilatation < 7
cm at time of epidural request.
Exclusions: regional contraindicated, previous systemic opioids, prostaglandins for cer-
vical ripening, amniotic infection, maternal or fetal medical conditions
Interventions All women received 10 mL/kg crystalloid prior to epidural insertion

Epidural (n = 36): initial bolus 10 mL bupivacaine 0.125% + sufentanil 10 µg. After at
least 20 minutes, with request for additional analgesia, boluses of bupivacaine of varying
concentration were administered; 0.125% until 7 cm cervical dilatation, then 0.25% at
8 to 9 cm and 0.5% in second stage
CSE (n = 41): single space, needle-through-needle. IT injection bupivacaine 2.5 mg +
sufentanil 2.5 µg. Subsequent epidural boluses as above
Outcomes Primary outcomes: prolonged fetal heart rate decelerations (decrease of 15 bpm for 2
to 10 minutes or baseline < 100) and increase uterine tone (10 mmHg) in the first
15 minutes after injection. Secondary outcome maternal hypotension (systolic < 100
mmHg or 20% fall). VAS (0 to 10) pain scores assessed; mean scores at 5, 10,15 and
20 minutes post-injection. Intervention failures reported and percentage of caesarean
births. Neonatal assessment by Apgar scores at 1 and 5 min and pH

Abrao 2009 (Continued)
Notes Brazil.
Risk of bias
Random sequence generation (selection Low risk Computer-generated random numbers is

bias) appropriate.
Allocation concealment (selection bias) Low risk Sealed, opaque envelopes allocated by in-
dependent person via a sequentially num-
bered series
Blinding (performance bias and detection Low risk Management and outcome assessors
bias) blinded.
All outcomes
Incomplete outcome data (attrition bias) High risk Of those originally randomised, 15% were
All outcomes not analysed; for neonatal pH this was 29%
Selective reporting (reporting bias) Low risk The primary and secondary outcomes were
reported.
Bhagwat 2008
Methods Randomisation: using a computer-generated randomisation list

Blinding: progress of labour was assessed by an obstetrician who was blinded, observations
were made by another anaesthetist who was not present at the time of procedure
Participants Inclusions: 60 nulliparous women in labour, cephalic, singleton with cervical dilatation
4 to 5 cm
Exclusions: cervical dilatation more than 5 cm, non vertex presentation, contraindication
to neuraxial analgesia
No. lost to follow-up: 1 (CSE group) went for emergency caesarean section
Interventions All women received 10 mL/kg crystalloid prior to epidural insertion

Epidural (n = 30): test dose 3 mL 1.5% lidocaine plus 15 µg of epinephrine, followed
by 10 mL bupivacaine 0.062% plus 0.0002% fentanyl. After 10 minutes an epidural
infusion of 0.0625% bupivacaine plus 0.0002% fentanyl was started using a patient
controlled analgesia pump at a rate of 8 to 12 mL/hr and titrated to maintain sensory
level of T10
CSE (n = 30): single space, needle-through-needle, sitting or lateral position. IT injection
of 1.25 mg bupivacaine + fentanyl 25 µg. Then after 10 minutes an epidural infusion of
0.0625% bupivacaine plus 0.0002% fentanyl was started using PCEA pump at the rate
of 8 to 12 mL/hr to maintain T10 sensory block

Bhagwat 2008 (Continued)
Outcomes Maternal: VAS pain < 3 at 30 minutes post block and the number of women requiring
additional analgesia and those who were satisfied on a 4-point scale. Number requiring
caesarean birth and the occurrence of hypotension, nausea/vomiting and pruritus noted.
Neonatal assessment by Apgar scores, cord blood gas analysis and need for admission to
the neonatal unit
Notes One still birth in the CSE group was excluded (cord around the neck)
Risk of bias
Random sequence generation (selection Low risk Used a computer-generated randomisation

bias) list.
Allocation concealment (selection bias) Unclear risk Not stated.
Blinding (performance bias and detection Low risk Progress of labour was assessed by an obste-
bias) trician who was blinded, observations were
All outcomes made by another anaesthetist who was not
present at the procedure and presumably
blinded
Incomplete outcome data (attrition bias) Low risk All of the parturients were followed up.
All outcomes
reported.
Other bias Unclear risk The study has not dealt with one still birth
in the CSE group (cord around neck), ex-
cluded from study
Breen 1999
Methods Randomisation: computer-generated randomisation in blocks of 4 with allocation con-

cealed in sealed envelopes
Blinding: procedure performed by an anaesthesiologist not involved in subsequent as-
sessments. Both assessor and participant blinded to allocation
Criteria for rescue analgesia: not specifically stated.
Statistics were not performed on an intention-to-treat basis. One woman in the epidural
group was excluded due to loss of blinding, and data from this participant were not used
in analysis
Participants Inclusions: 41 participants were initially enrolled into the study, all ASA class 1 or 2, at
least 18 years old, with a singleton fetus with cervical dilatation < 6 cm
Exclusions: inability to give informed consent, allergy to study drugs and contraindica-
tion to regional blockade

Breen 1999 (Continued)
No. lost to follow-up: 1 woman in epidural group dropped from analysis due to loss of
blinding
Interventions Epidural (n = 20): all women received 750 to 1000 mL crystalloid prior to epidural
insertion. The initial epidural bolus was a 3 mL test dose of 1.5% lidocaine with 1:200,
000 epinephrine. This was followed 3 min later with a bolus 100 µg fentanyl diluted to
a volume of 10 mL with saline down the epidural catheter. The study period ended with
the first request for additional analgesia
CSE (n = 21): single space, needle-through-needle. An intrathecal injection of sufentanil
10 µg diluted to 2 mL with saline. The epidural catheter was placed in the same manner
as for the epidural group, but no drugs were given down it until additional analgesia was
requested, at which point the study period ended
Outcomes Primary outcome was time from injection of narcotic until request for additional analgesia
(duration of analgesia).
VAS pain scores were assessed at 0, 5, 10, 15 and 30 min, and thereafter every 30 min.
Motor block on Bromage scale was assessed at 30 min. Ability to walk and void urine
was only assessed in those with full motor power. The incidence of itch was assessed by
VAS scores
Notes Canada.
Risk of bias
Random sequence generation (selection Low risk Computer-generated randomisation in

bias) blocks of 4.
Allocation concealment (selection bias) Low risk Used opaque, sealed envelopes.
Blinding (performance bias and detection Low risk Double-blinded, both women and the
bias) anaesthesiologist collecting the data were
All outcomes blinded
Incomplete outcome data (attrition bias) Low risk One woman in epidural group dropped
All outcomes from analysis due to loss of blinding
Selective reporting (reporting bias) Low risk Primary and secondary outcomes were re-
ported except for one epidural group pa-
tient

Caldwell 1994
Methods Randomisation: not stated. “Patients were randomly assigned...”.

Blinding: not mentioned at all anywhere in the paper.
Follow-up request: “Randomisation was by computer-generated random numbers. Se-
quentially numbered, sealed envelopes prepared by a non-investigator. Participant and
anesthesiologist-investigator were blinded to treatment group; upon opening the sealed
envelope, a non-investigator anesthesiologist confidentially prepared the study drug for
administration.”
Criteria for rescue analgesia: no specific mention of rescue analgesia per se. On request
for additional analgesia, participants in the CSE group were given 10 mL bupivacaine 0.
25% and then an infusion of bupivacaine 0.125% with fentanyl 10 µg/mL was started.
Women in the epidural group received an infusion immediately after the initial bolus of
bupivacaine 0.125% with sufentanil 100 µg/mL. No mention made of additional rescue
analgesia
No participants were lost to follow-up and data from all were included in the statistical
analysis
Participants Inclusions: all women were ASA class 1 in labour with a singleton fetus
Exclusions: none stated.
No. lost to follow-up = 0.
Interventions Epidural: 33 women received epidural analgesia, initiated with 10 mL bupivacaine 0.

25% and sufentanil 10 µg. This was followed immediately by an infusion of bupivacaine
0.125% with sufentanil 0.2 µg/mL
CSE: 26 women had CSE analgesia initiated in a single space, needle-through-needle
technique (18 G, 24 G Sprotte). An initial intrathecal injection of morphine sulphate 0.
25 mg and fentanyl 25 µg. Nothing was given down the epidural catheter until a request
for additional analgesia, at which time a bolus of 10 mL bupivacaine 0.25% was given
and followed immediately by an infusion of bupivacaine 0.125% with fentanyl 1 µg/mL
Outcomes Maternal: blood pressure and heart rate recorded every 15 min until delivery. The oc-
currence of nausea/vomiting, pruritus, PDPH and respiratory depression was noted.
Mode of delivery was noted as either “normal” or “operative”, i.e. either caesarean or
instrumental
Neonatal: Apgar scores and umbilical arterial and venous pH.
Notes USA.
Risk of bias
Random sequence generation (selection Low risk Randomisation was by computer-gener-

bias) ated random numbers.
Allocation concealment (selection bias) Low risk Upon opening the sealed envelope, a
non-investigator anaesthesiologist confi-
dentially prepared the study drug for ad-
ministration

Caldwell 1994 (Continued)
Blinding (performance bias and detection Unclear risk Not stated.

bias)
All outcomes
Incomplete outcome data (attrition bias) Low risk No loss to follow-up.

All outcomes
Selective reporting (reporting bias) Low risk Primary and secondary outcomes reported.
Cohen 2006
Methods Parturients who requested epidural analgesia were randomised
Participants Inclusions: 136 parturients who requested epidural analgesia for labour pain
No. lost to follow-up: 5 CSE women were removed from the study following failure to
pierce the dura - and presumably were replaced to leave 68 in both groups. The data
from the successful women were included
Interventions Epidural: 68 women received 20 mL ropivacaine 0.04% (8 mg) with adrenaline and
sufentanil 1 µg/mL (20 µg) followed by PCEA using same solution with 4 mL bolus and
10 minute lockout plus background infusion of 4 mL/hr
CSE: 68 women received ropivacaine 2 mg with sufentanil 5 µg intrathecally followed
by PCEA as above
Both groups received rescue of 0.25% ropivacaine from 20 minutes if VAS > 3
Outcomes Maternal: time from first injection to maximal analgesia; the number who mobilised; the
occurrence of hypotension and pruritus and the need for bladder catheterisation. Fetal
bradycardia during the fist 30 minutes after block was also noted (this is not an outcome
for this review)
Neonatal: Apgar scores (actual scores not available).
Notes USA. Abstracts only: 2004, 2004 and 2006.
Risk of bias
Random sequence generation (selection Unclear risk Parturients “were randomized”.

bias)

bias)
All outcomes

Cohen 2006 (Continued)
Incomplete outcome data (attrition bias) Low risk Data for the women who completed the
All outcomes study were available.
reported.
COMET 2001a
Methods Randomisation: using a customised randomisation programme provided by clinical trials

experts
Blinding: participant not blinded. Assessor only blinded with respect to obstetric man-
agement
Criteria for rescue: in the traditional 0.25% bupivacaine (higher-dose) group rescue given
as fentanyl 50 µg or more concentrated bupivacaine. For CSE and low-dose infusion (0.
1% bupivacaine = fentanyl 2 µg/mL) a further 10 mL of this solution was used or 0.
25% bupivacaine if necessary
Statistical analysis was performed on an intention-to-treat basis. Separate comparisons
between mobile techniques and traditional group
Participants Inclusions: 1054 nulliparous women in labour.

Exclusions: contraindication to epidural analgesia, previous epidural or spinal procedure,
imminent delivery, injection of pethidine within the previous 4 hours
No. lost to follow-up (post partum interview): 13.
Interventions Epidural (n = 353): test dose 3 mL 2% lidocaine (60 mg) followed after 5 min with 10
mL bupivacaine 0.25%. Subsequent boluses of 10 mL bupivacaine 0.25% on request
Low-dose infusion (n = 350): bolus of 15 mL bupivacaine 0.1% with fentanyl 2 µg/mL,
followed by an infusion of the same at 10 mL/hr
CSE (n = 351): single space, needle-through-needle, sitting or lateral position. IT injec-
tion of 2.5 mg bupivacaine + fentanyl 25 µg. Then epidural boluses of 15 mL bupiva-
caine 0.1% + fentanyl 2 µg/mL on request
Outcomes Primary outcome measure mode of delivery. Secondary outcomes progress of labour
(duration of first and second stages), oxytocin augmentation, regular pain assessments
(VAS), women’s perceptions of their ability to push and urinary retention
Neonatal assessments of Apgar scores at 1 and 5 min, resuscitation requirements and
admission to the special care unit. Birthweight was recorded after delivery
Notes UK.
Funded by grants from the NHS Research and Development Mother and Child Health
Programme
Risk of bias

COMET 2001a (Continued)
Random sequence generation (selection Low risk Used a customised randomisation pro-
bias) gramme.
Allocation concealment (selection bias) Low risk The study group code was not revealed be-
fore completion of recruitment
Blinding (performance bias and detection High risk The participants and those in attendance
bias) were not blinded. Trial midwives assessing
All outcomes VAS 24 hours after delivery were blinded
to obstetric management
Incomplete outcome data (attrition bias) Low risk Total number lost 13 (of 1054 randomised)
All outcomes .
ported.
Cortes 2007
Methods Randomisation: method not stated, “randomly divided into two groups”
Blinding: not stated.
Participants Inclusions: 40 women, singleton, term in labour at 4 to 5 cm dilatation

No. lost to follow-up: 0
Interventions Epidural: 20 women received 8 mL bupivacaine 0.25% (20 mg) with adrenaline and fen-
tanyl 100 µg followed by intermittent bolus of 4 mL bupivacaine 0.25% with adrenaline
as required
CSE: 20 women received fentanyl 25 µg intrathecally followed by intermittent epidural
boluses as above
Supplementation of 6 mL was available for both groups for delivery
Outcomes Maternal: VAS scores at 0, 5, 10, 15 and 20 minutes post initial injection; the number who
mobilised; the occurrence of hypotension, pruritus, respiratory depression and nausea/
vomiting. The mode of delivery was also noted
Neonatal: Apgar scores.
Notes Brazil - translated.
Risk of bias

Cortes 2007 (Continued)
Random sequence generation (selection Unclear risk Stated only, “randomly divided into two
bias) groups”.

bias)
All outcomes
Incomplete outcome data (attrition bias) Low risk All the data are available.
All outcomes
Selective reporting (reporting bias) Low risk Outcomes are all reported.
Dunn 1998
Methods Randomisation: method not stated. “Patients were randomised into 2 groups.”
Blinding: outcome assessor blinded.
Criteria for rescue analgesia: if inadequate analgesia after 20 min, 15 mL bupivacaine
0.125% given down epidural, followed by 10 mL lidocaine 2% if needed. If this was
ineffective then catheter replaced and data excluded from analysis
Statistical analysis not performed on an intention-to-treat basis
Participants Inclusions: 70 healthy ASA 1 or 2 women in early labour (cervical dilatation < 5 cm)
Exclusions: history of previous caesarean section or IV opioids before requesting epidural
analgesia
Interventions Epidural (n = 35): test dose 3 mL lidocaine 1.5% + 1:200,000 epinephrine. Then bolus
sufentanil 40 µg in 10 mL saline down epidural catheter. Study ended at request for
additional analgesia
CSE (n = 34): single space, needle-through-needle, sitting. IT injection sufentanil 10
µg diluted to 1 mL. Epidural catheter sited but nothing administered down it until
requested, at which point study ended
Outcomes VAS pain scores and severity of side effects assessed at 5, 10, 15, 20 and 30 min, and
thereafter every 30 min. Maternal blood pressure, pulse and respiratory rate, and motor
block were assessed at the same times. Time of request for additional analgesia noted and
study ended. Mode of delivery noted and incidence of PDPH recorded.
Neonate assessed by Apgar scores.
Notes USA.
Risk of bias

Dunn 1998 (Continued)
Random sequence generation (selection Unclear risk Stated, “randomised into 2 groups”.
bias)
Blinding (performance bias and detection Low risk Stated, “observations were made by an indi-
bias) vidual blinded to the analgesic technique”
All outcomes
Incomplete outcome data (attrition bias) Low risk One patient lost to follow-up.
All outcomes
Gomez 2001
Methods Randomisation: method not stated.

Blinding: stated as “single blinded” study but unclear as to specifically whether the
outcome assessor was blinded to allocation
Criteria for rescue analgesia: when VAS pain score 3 or greater, 4 mL bolus bupivacaine
0.25% administered. Minimum 30 min between injections
Nil lost to follow-up.
Participants Inclusions: 42 ASA 1 or 2 women in spontaneous labour with a singleton, vertex pre-
sentation fetus. Cervical dilatation 2 to 5 cm
Exclusions: obstetric pathology, meconium stained liquor, ruptured membranes, previous
caesarean section
Interventions Epidural (n = 21): test dose 3 mL bupivacaine 0.25% + adrenaline 1:200,000 followed
by 5 mL of the same solution. Immediate infusion of bupivacaine 0.125% with fentanyl
1 µg/mL at 8 mL/hr
CSE (n = 21): sitting, otherwise technique not stated. IT injection of bupivacaine 2.5
mg + 25 µg fentanyl + adrenaline 1:200,000. Once VAS of 3 to 4, 8 mL bupivacaine
0.125% + adrenaline 1:200,000 and an infusion of the same solution and rate as the
epidural group
Outcomes Maternal: VAS pain scores at 5, 10, 15 and 30 min and then hourly. At the same
time intervals sensory block to pinprick and motor block (Bromage scale) were assessed.
Number of additional rescue analgesia boluses was noted. VAS maternal satisfaction
recorded at delivery. Presence of arterial hypotension (decrease from baseline of greater
than 20%) was documented. Maternal bradycardia (rate less than 60 bpm) was noted.
Adverse effects noted: nausea and vomiting, pruritus. Mode of delivery recorded as
normal, instrumental or caesarean
Neonatal: occurrence of fetal bradycardia less than 100 bpm noted. No recorded neonatal
assessments

Gomez 2001 (Continued)
Notes Spanish (translated).
Risk of bias
Random sequence generation (selection Unclear risk “The patients were divided randomly into
bias) two groups”.
Blinding (performance bias and detection Unclear risk Not stated, except “prospective, ran-
bias) domised, blinded study”.
All outcomes

All outcomes
Selective reporting (reporting bias) Low risk Primary and secondary outcomes are
stated.
Goodman 2006
Methods Randomisation: computer-generated randomisation table, placed in opaque envelope

Blinding: the women and the nurses caring for the patient and the outcome investigator
were blinded
Criteria for rescue analgesia: if after 15 minutes post epidural or spinal dose still had
inadequate pain relief, 5 mL bolus of bupivacaine 0.25% was administered via the
epidural catheter
Participants Inclusions: 100, ASA 1 to 2, parous (1 or more prior vaginal delivery) women at term
in early labour (< 5 cm cervical dilatation)
Exclusions: women with severe scoliosis, BMI > 45, any contraindication to neuraxial
analgesia, or were taking other pain medication
No. excluded: 16 (9 protocol violations which included 5 in CSE group and 4 in epidural
group. 2 women had missing data (1 in each group), 2 spinal anaesthetics resulted in
only partial drug administration (CSE group) and 3 epidural catheters failed
Interventions Epidural (n = 41) 3 mL test dose of 0.25% bupivacaine followed 5 min later by 10 mL
of bupivacaine 0.125% with fentanyl 50 µg
CSE (n = 43): single space, needle-through-needle, 17 gauge Touhy needle and 27 gauge
Whitacre needle, intrathecally bupivacaine 2.5 mg and fentanyl 25 µg
Both groups were commenced on a continuous infusion of bupivacaine 0.0625% with
fentanyl 2 µg/mL at 12 mL/hr within 15 min of administration of the spinal or epidural
dose

Goodman 2006 (Continued)
Outcomes Maternal: VAS (0 to 10) pain scores at 10 and 30 minutes post procedure and the number
with VAS > 3 at 10 minutes; hypotension, pruritus, number requiring caesarean section.
Maternal satisfaction with analgesia recorded. Total failures of primary technique were
also documented. No neonatal outcomes
Notes
Risk of bias
Random sequence generation (selection Low risk Stated, “using computer generated ran-
bias) domisation table”.
Allocation concealment (selection bias) Low risk Opaque envelopes were used for allocation.
Blinding (performance bias and detection Low risk The subject and the investigator were
bias) blinded.
All outcomes
Incomplete outcome data (attrition bias) Low risk Similar numbers were not analysed from
All outcomes both groups - a total of 16 of 100
Selective reporting (reporting bias) Low risk The primary and secondary outcomes are
available.
Hepner 2000
Methods Randomisation: method not stated “randomised to either technique”.

Follow-up request: “1. randomisation: random-number table, 2. allocation concealment:
sequentially-numbered, sealed, opaque envelopes, 3. blinding: the resident performing
the technique was aware of the group assignment but the staff evaluating the outcome
was not”
Blinding: mother and outcome assessor blinded.
Criteria for rescue analgesia: inadequate analgesia at 20 min treated with 13 mL bupiva-
caine 0.0625% + fentanyl 2 µg/mL + 0.05 mL sodium bicarbonate 8.4% + epinephrine
1:200,000
Data from all participants analysed as no loss from study.
Participants Inclusions: “healthy term parturients”.

Exclusions: pregnancy-induced hypertension, diabetes, preterm labour, bleeding prob-
lems, scoliosis, cervical dilatation > 5 cm, previous IV opioid

Hepner 2000 (Continued)
Interventions Epidural (n = 24): 16 mL bupivacaine 0.0625% + fentanyl 2 µg/mL + 0.05 mL NaHCO3

8.4% + epinephrine 1:200,000 (BFSE). At request for additional analgesia further bolus
13 mL and infusion started of bupivacaine 0.0625% + fentanyl 2 µg/mL + epinephrine
1:400,000 at 10 mL/hr
CSE (n = 26): single space, needle-through-needle, sitting. IT LA bupivacaine 2.5 mg +
fentanyl 25 µg. On request for additional analgesia 13 mL BFSE (see above) and infusion
commenced at 10 mL/hr as above
Outcomes Maternal blood pressure, heart rate and haemoglobin saturation, and fetal heart rate and
uterine activity monitored throughout labour. VAS pain scores. Parturient satisfaction
at delivery and day 1 postpartum. Motor block at 15 and 30 min. Times: infiltration -
catheter taping - initial analgesia - request for additional analgesia. Need for supplemental
analgesia, treatment of hypotension, pruritus, nausea/vomiting. Hypotension defined
as reduction in systolic blood pressure to < 100 mmHg or reduction of > 30% from
baseline. Fetal heart rate changes.
Neonatal Apgar scores, umbilical arterial and venous pH.
Notes USA.
Risk of bias
Random sequence generation (selection Low risk A random number table was used.
bias)
Allocation concealment (selection bias) Low risk Used sequentially numbered, sealed,
opaque envelopes.
Blinding (performance bias and detection Low risk “Another anaesthesiologist, blinded to the
bias) technique, was in charge of collecting the
All outcomes data”
Incomplete outcome data (attrition bias) Low risk 2 in each group delivered before initial
All outcomes block wore off and not included in dura-
tion analysis
Selective reporting (reporting bias) Low risk Primary and secondary outcomes are re-
ported.

Kartawiadi 1996
Methods Randomisation: method not stated “63 ASA class 1-3 parturients...randomly assigned..
.”.
Blinding: outcome assessor blinded to allocation.
Follow-up request 2006: “randomisation was done with randomisation tables and the
sequence of allocation was put in separate numbered envelopes. After the procedure these
were resealed and kept by the third author until the end of the study”
Criteria for rescue analgesia: not stated.
No loss of participants from the study so all included in statistical analysis. NB 13
delivered before requesting additional analgesia and so were not included in statistics for
duration of analgesia
Participants Inclusions: 63 ASA 1-3, singleton, vertex at 36-41 weeks’ gestation. In active labour with
cervical dilatation < 5 cm at time of epidural request.
Exclusions: history of hypertension or pre-eclampsia.
No. lost to follow-up: 13 for duration data, 0 for all other parameters
Interventions Epidural (n = 31): initial bolus 10 mL bupivacaine 0.125% + sufentanil 10 µg +

epinephrine 12.5 µg. On request for additional analgesia 10 mL boluses of same were
delivered down the catheter
CSE (n = 32): single space, needle-through-needle, lateral. IT injection bupivacaine 1.
0 mg + sufentanil 5 µg + epinephrine 25 µg. Immediate epidural bolus 10 mL saline
given. On request for additional analgesia, same 10 mL bolus given as for the epidural
group (see above)
Outcomes Maternal blood pressure and ECG monitoring. VAS (0 to 10) pain scores assessed. Time
to VAS < 2.5 or < 50% baseline taken as onset. Total dose of local anaesthetic required and
adverse effects. Sensory and motor block assessed post injection. Maternal satisfaction
with analgesia recorded. Neonatal assessment by Apgar scores at 1 and 5 min
Notes Belgium.
Risk of bias
Random sequence generation (selection Low risk Used randomisation tables.

bias)
Allocation concealment (selection bias) Low risk Used separate sealed numbered envelopes.
Blinding (performance bias and detection Low risk The investigating anaesthesiologist was dif-
bias) ferent to the one performing the block
All outcomes
Incomplete outcome data (attrition bias) Low risk 13 (of 63 randomised; 7 in one and 6 in
All outcomes the other group) delivered before request-
ing additional analgesia and were not in-
cluded in duration analysis; all others in-
cluded

Kartawiadi 1996 (Continued)
ported.
Medina 1994
Methods Randomisation, allocation concealment, blinding and assessment bias are all unclear
Participants Inclusions: 28 women 3 to 5 cm dilatation, primigravid.

No. lost to follow-up: 2, 1 complete failure in each group.
Interventions Epidural (n = 12): initial bolus 10 mL 0.125% bupivacaine, plus 10 µg sufentanil.

CSE: 3.75 mg bupivacaine plus 3 µg sufentanil.
Both groups given ED infusion after reappearance of pain: 7 to 10 mL/hour of 0.125%
bupivacaine plus 0.5 µg/mL sufentanil
Outcomes Maternal: VAS pain scores at 5, 10, 30, 60, 75, 90, 120, 150, 180, 210, 240 minutes.
Adverse effects; itch, vomiting, hypotension, high block, bradycardia, reflex sympathetic
pain
Notes Italy. Poster from ASRA meeting.
Risk of bias
Random sequence generation (selection Unclear risk “Patients randomly allocated”.

bias)

bias)
All outcomes
Incomplete outcome data (attrition bias) Low risk One in each group lost to follow-up (one
All outcomes in each group was excluded for complete
failure)
Selective reporting (reporting bias) Unclear risk Primary and secondary outcomes were not
stated.

Ngamprasertwong 2007
Methods Randomisation: “a sealed-envelope technique”.

Blinding: single-blinded: obstetric residents and labour nurses managed the labours
according to standardised protocols and were unaware of the anaesthetic administration
Rescue analgesia 10 mL of 0.25% bupivacaine if inadequate analgesia after 20 min of
initial analgesia
No losses to follow-up and all were included in statistical analysis
Participants Inclusions: 50 women, nulliparous and multiparous, healthy, full term, in labour
Exclusion: twins, pregnancy induced hypertension, placenta praevia, regional contraindi-
cation
Interventions Epidural (n = 25): crystalloid preload (quantity not stated). Test dose 3 mL of 0.25%
bupivacaine plus bolus of 7 mL of 0.25% bupivacaine. Then infusion of 0.0625%
bupivacaine with fentanyl at 12 mL/hr started immediately
CSE (n = 25): crystalloid preload. Single space, needle-through-needle, using Quicke 27
G needle. 25 µg of fentanyl injected intrathecally. Epidural catheter was inserted and 3
mL of 0.25% bupivacaine given as test dose, 0.0625% bupivacaine with fentanyl 2 µg/
mL was infused at 12 mL/hr
Outcomes Primary: onset of effective analgesia. Secondary: motor blockade, mode of delivery and
side effects
Notes Quinke needles used (27G). Thailand.
Risk of bias
Random sequence generation (selection Unclear risk No mention of the actual randomisation
bias) method.
Allocation concealment (selection bias) Low risk Sealed envelopes were used.
Blinding (performance bias and detection High risk Labour attendants were unaware but asses-
bias) sors were not.
All outcomes
Incomplete outcome data (attrition bias) Low risk No loss to follow-up

All outcomes
ported.

Nickells 2000
Methods Randomisation: sealed envelopes.

Blinding: participant and midwife blinded to allocation. Assessment of motor block and
proprioception made by an unblinded anaesthetist
Criteria for rescue analgesia: any participants with persistently painful contractions at
30 min were treated at the discretion of the anaesthetist to ensure adequate analgesia
Unclear if statistical analysis was performed on an intention-to-treat basis
Participants Inclusions: 142 women in established labour, gestation at least 36 weeks, singleton,
cephalic fetus
Exclusions: pethidine within 4 hours of requesting epidural analgesia
No. lost to follow-up: there were 18 analgesic failures (9 in each group) but were included
in analysis for outcomes other than time to effective analgesia
Interventions Epidural (n = 73): initial bolus 10 mL bupivacaine 0.125% + fentanyl 50 µg. Further
boluses 10 mL bupivacaine 0.1% + fentanyl 2 µg/mL given on request for additional
analgesia
CSE (n = 69): single space, needle-through-needle, sitting.
IT injection bupivacaine 2.5 mg + fentanyl 25 µg. Additional analgesia provided on
request as for the epidural group
Outcomes Analgesia onset measured as time to first “comfortable” contraction. Maternal blood
pressure every 5 min for 20 min (hypotension defined as decrease in SBP < 100 mgHg)
. Continuous fetal heart monitoring with fetal bradycardia < 100 bpm noted.
At 30 min assessment of motor block and proprioception.
Notes UK.
Risk of bias
Random sequence generation (selection Unclear risk Not stated.

bias)
Allocation concealment (selection bias) Low risk Used sealed envelopes.
Blinding (performance bias and detection Low risk Midwife who assessed the speed of onset
bias) and pain was blinded
All outcomes
Incomplete outcome data (attrition bias) High risk There were 18 analgesic failures (9 in each
All outcomes group); all other data outcomes complete
ported.
Other bias Unclear risk Study stopped after 3 months so slightly

uneven group sizes.

Parry 1998
Methods Randomisation: method not stated. “patients....were randomly allocated...”

Blinding: assessments made by an anaesthetist blinded to group allocation and treatment
Criteria for rescue analgesia: not mentioned.
No participants were lost to follow-up and data from all participants were included in
analysis
Participants Inclusions: ASA 1 or 2 women at term requesting analgesia in the first stage of labour or
elective LSCS under regional.
Exclusions: pre-existing neurological impairment or diabetes mellitus
Interventions Epidural (n = 30): all women were preloaded with 500 to 1000 mL crystalloid prior to
epidural insertion while sitting. Initial bolus 15 mL bupivacaine 0.1% with fentanyl 2
µg/mL
CSE (n = 30): fluid preloading as for the epidural group. Single space, needle-through-
needle, sitting. Intrathecal injection of bupivacaine 2.5 mg + fentanyl 25 µg in a total
volume 2.5 mL. Epidural catheter placed for subsequent analgesia (after study period)
Outcomes ’Routine’ measurement of maternal and fetal heart rates and maternal blood pressure
were performed in all groups. (Hypotension was defined as a decrease in systolic blood
pressure to < 100 mmHg or of > 20% from baseline.)
Assessment of sensory and motor block and dorsal column modalities was performed
20 to 30 min after initial injection. Normal delivery rate was recorded in each group.
Assessment was made for spinal headache and neurological complications
LSCS group was analysed as a separate subgroup, enabling comparison of CSE and ED
subgroups
Neonatal assessment was by Apgar scores at 5 min.
Notes UK.
Risk of bias
Random sequence generation (selection Unclear risk Not stated: “patients were randomly allo-
bias) cated”.
Blinding (performance bias and detection Low risk Outcome assessor blinded.
bias)
All outcomes

All outcomes

Patel 2003a
Methods Randomisation: method not stated, “...prospective, double-blind study and randomised.
..”.
Blinding: stated to be “double-blind”.
Criteria for rescue: not stated.
Participants Inclusions: 115 healthy women, 2 to 6 cm dilatation requesting regional.

Exclusions: not stated.
2 lost to CTG analysis.
Interventions Epidural (n = 53): all women received initial bolus 20 mL bupivacaine 0.1% + fentanyl
40 µg.
CSE: all women received intrathecal bupivacaine 2.5 mg + fentanyl 5 µg.
Subsequent management: not stated.
Outcomes Maternal: mode of delivery (no results stated).

Fetal: umbilical artery pH and base excess; Apgars at 1 and 5 min; CTG abnormalities
Notes UK. Abstract only.
Risk of bias
Random sequence generation (selection Unclear risk Stated, “double blind study and ran-
bias) domised”, no other information
Blinding (performance bias and detection Unclear risk Stated to be double-blind.

bias)
All outcomes
Incomplete outcome data (attrition bias) Low risk 2 lost to CTG analysis.
All outcomes
Selective reporting (reporting bias) Unclear risk Reporting of detail of outcomes is unclear.
Price 1998
Methods Randomisation: sealed and numbered envelopes.

Blinding: mother and outcome assessments.
Criteria for rescue: additional analgesia delivered as 10 mL bupivacaine 0.25%.
Statistics not performed on intention-to-treat basis.
Participants Inclusions: 100 women in labour cervix < 6 cm dilated.

Exclusions: pethidine < 3 hr before epidural request, pregnancy-induced hypertension.

Price 1998 (Continued)
Interventions Epidural (n = 48): 15 mL bupivacaine 0.1% + fentanyl 75 µg bolus then PCEA 10 mL

bupivacaine 0.1% + fentanyl 2 µg/mL with 30 min lockout
CSE (n = 45): single space, needle-through-needle, lateral position, IT LA: 2.5 mg
bupivacaine + 25 µg fentanyl then PCEA 15 mL 0.1% bupivacaine + fentanyl 2 µg/mL,
30 min
Outcomes Pain scores and motor block at 0, 30, 60, 180 min.
Maternal confidence in walking.
Time to first epidural top-up and need for additional analgesia.
Adverse effects: hypotension (no definition given), pruritus, need for urinary catheteri-
sation.
Maternal satisfaction postpartum #1.
Notes UK.
Risk of bias
Random sequence generation (selection Unclear risk Method of randomisation not stated.
bias)
Allocation concealment (selection bias) Low risk Used “sealed, numbered envelopes”.
Blinding (performance bias and detection Low risk The patient and the investigator were
bias) blinded.
All outcomes
Incomplete outcome data (attrition bias) Low risk There was no loss to follow-up and drop
All outcomes out was similar in both groups (7 in total)
ported.
Roux 1999
Methods Randomisation: by drawing lots.

Blinding: states “double blinded for all assessments not involving problems at perfor-
mance of block”
Criteria for rescue: not mentioned.
Data not analysed on an intention-to-treat basis. (NB all participants’ data included for
complications on insertion.)

Roux 1999 (Continued)
Participants Inclusions: 80 women between 37 and 42 weeks’ gestation, in active labour with cervical
dilatation not more than 3 cm. All with singleton, cephalic fetus
Exclusions: any contraindication to CSE or epidural.
No. lost to follow-up: 1 participant not included as failure to site CSE successfully. Data
used only in analysis regarding complications at insertion
Interventions Epidural (n = 40): all given 500 mL crystalloid prior to insertion of epidural in the sitting
position. Initial bolus given down the catheter of 6 to 8 mL bupivacaine 0.25% with
sufentanil 20 µg. Top-up boluses were delivered on request of 6 to 8 mL bupivacaine 0.
25%
CSE (n = 39): sitting, single space, needle-through-needle (18 G, 29 G). Initial bolus
IT sufentanil 10 µg in total volume 3 mL with isotonic saline. Top-up bolus given down
epidural catheter when requested, as 6 to 8 mL bupivacaine 0.25% in increments of 2
to 3 mL
Outcomes Pain scores assessed on VAS 0 to 10 at injection, then 5, 10, 15, 20, 30 min and thereafter
every 30 min. Complete analgesia was defined as a VAS score = 0. Time from initial bolus
to first top-up request was noted as bolus duration. The incidence of complications at
time of insertion was recorded. Maternal systolic blood pressure and oxygen saturation
were recorded. (Hypotension was defined as SBP of 90 mmHg or lower and was corrected
with IV fluid bolus.) Continuous cardiotocograph recording was taken throughout the
labour. The duration of first and second stages of labour were noted and the mode of
delivery. The occurrence of itch, nausea, vomiting and sedation was noted at the same
times as VAS pain. Incidence of headache was assessed on the third postpartum day
Neonatal assessment by Apgar scores at 1 and 5 min.
Notes France (translated).
Risk of bias
Random sequence generation (selection Unclear risk Allocation by drawing lots.

bias)
Blinding (performance bias and detection Low risk Double-blinded or single-blinded if prob-
bias) lem in performing the block
All outcomes
Incomplete outcome data (attrition bias) Low risk One participant not included as failure to
All outcomes site CSE successfully. Data used only in
analysis regarding complications at inser-
tion
reported.

Roux 1999 (Continued)
Sezer 2007
Methods Randomisation: “prospectively randomized” using closed envelope allocation into 2

groups
Participants Inclusions: 40 nulliparous women ASA 1 at term with singleton, cephalic fetus, in
spontaneous labour with cervical dilatation less than 6 cm
Interventions Epidural (n = 20): test dose of 3 mL of lignocaine 1.5% plus adrenaline, then 7 mL bolus
of 0.1% bupivacaine plus fentanyl 50 µg
CSE (n = 20): intrathecal dose of fentanyl 20 µg in 1.5 mL of saline plus epidural test
dose of 3 mL of 1.5% lignocaine plus adrenaline after 45 minutes
Both groups were maintained with PCEA of 5 mL bolus of bupivacaine 0.1% plus
fentanyl 2 µg/mL on demand with lockout of 10 minutes and maximum of 15 mL in 1
hour
Outcomes Maternal: time from injection to VAS (0 to 10) pain score of less than or equal to 3.
Maternal satisfaction with analgesia and number with pruritus and nausea and vomiting;
mode of delivery. Neonatal outcomes: mean Apgar score at 5 minutes
Notes
Risk of bias
Random sequence generation (selection Unclear risk “Prospectively randomized”.

bias)
Allocation concealment (selection bias) Low risk “Closed envelope allocation”.
Blinding (performance bias and detection Unclear risk No mention of blinding.

bias)
All outcomes
Incomplete outcome data (attrition bias) Low risk There is no loss to follow-up.
All outcomes
ported.

Skupski 2009
Methods Randomisation: used web-based randomisation software for 200 women divided into 2
blocks of 100 without stratification. Allocation concealment using opaque, sequentially
numbered, sealed envelopes kept off-site
Blinding: no blinding of subjects or investigators.
Statistical analysis was performed on an intention-to-treat basis
Participants Inclusions: 127 women, 18 to 50 years old, term, cephalic, singleton, BMI < 40, with
or without induction
Exclusions: morbid obesity, non reassuring fetal heart rate pattern, planned caesarean,
hypertension for any reason, significant obstetric medical condition
Interventions All women received 1 litre of intravenous fluid 30 to 40 min before block
Epidural (n = 63): 15 mL of bupivacaine 0.0625% plus fentanyl 2 µg/mL
CSE (n = 64): 1 mL of 0.25% bupivacaine plus fentanyl 20 µg intrathecally
Both groups received immediate infusion of bupivacaine 0.0625% plus fentanyl 2 µg/
mL at 12 mL/hr
Outcomes Primary outcome was prolonged deceleration of fetal heart rate and secondary outcomes
of fetal heart rate changes (which are not outcomes for this review)
Other maternal: VAS pain scores (1 to 10) every 2 minutes for 10 minutes after block
placement, then every 5 minutes for 20 minutes, then every 10 minutes for 30 minutes;
hypotension, pruritus, nausea and vomiting, back pain and urinary retention; number
requiring caesarean section. No neonatal outcomes
Notes
Risk of bias
Random sequence generation (selection Low risk Used website random number generator.
bias)
Allocation concealment (selection bias) Low risk Used sequen-

tially numbered, sealed, opaque envelopes
unavailable to those doing recruitment
Blinding (performance bias and detection High risk Blinding of the type of neuraxial block was
bias) not performed for either subjects or inves-
All outcomes tigators

All outcomes
ported.

Skupski 2009 (Continued)
Other bias Unclear risk Study is underpowered to detect the differ-

ence in fetal heart rate changes
Thomas 2005
Methods Randomisation: computerised random-number generator.

Blinding: outcome assessments blinded.
Criteria for rescue: top-ups of 5 mL 0.25% bupivacaine to 15 mL, then ED catheter
withdrawn 1 to 2 cm increments and then replaced
Participants Inclusions: 251 healthy, in labour, < 6 cm dilatation, uncomplicated pregnancies, re-
questing analgesia.
Exclusions: not stated.
Number lost to follow-up: 21, 20 from CSE group, 1 from ED group. A subgroup was
generated for analysis from 18 CSE participants where no CSF obtained
Interventions Epidural (n = 124): all given initial 10 mL divided dose 2% plain lignocaine via ED
catheter, then immediately commenced on PCEA
CSE (n = 127): dural puncture with 27 G Whitacre with nil intrathecal drugs; 10 mL
lignocaine as per ED group, followed immediately by PCEA as per ED group
PCEA: bupivacaine 0.11% + fentanyl 2 µg/mL at 10 mL per hour with 5 mL bolus and
10 minute lock-out
Outcomes Maternal: additional interventions, known dural tap, hypotension, labour augmentation,
mode of delivery
Notes USA. Institutional funding.
Risk of bias
Random sequence generation (selection Low risk Stated, “computerized random number
bias) generator”.
Blinding (performance bias and detection Low risk Outcome assessor and
bias) patient were blinded; unblinded operator
All outcomes performing the procedure recorded the ini-
tial parameters
Incomplete outcome data (attrition bias) Low risk 20 women were excluded (2 because of in-
All outcomes advertent dural puncture and 18 because
no CSF return from spinal needle). These
18 women were analysed in another sub-
group for separate data analysis and the data

Thomas 2005 (Continued)
are available
reported.
Tsen 1999
Methods Randomisation: sealed and numbered envelopes.

Blinding: both participant and outcome assessor blinded.
Rescue analgesia as either 6 mL bupivacaine 0.25% or fentanyl 50 µg in 10 mL saline
No losses to follow-up and all were included in statistical analysis
Participants Inclusions: 100 women, nulliparous, ASA 1 or 2, at term, in spontaneous labour with
singleton, cephalic fetus. Cervical dilatation < 5 cm
Exclusion: cervical dilatation > 5 cm.
Interventions Epidural (n = 50): 1000 mL crystalloid preload. “Dummy” spinal (no dural puncture)
before placement of catheter. Bolus 12 mL bupivacaine 0.25% then infusion bupivacaine
0.125% + fentanyl 2 µg/mL at 10 mL/hr
CSE (n = 50): 1000 mL crystalloid preload. Single space, needle-through-needle, lateral
position. IT injection bupivacaine 2.5 mg + sufentanil 10 µg. When requested, epidural
bolus given as 6 mL bupivacaine 0.25% then infusion of bupivacaine 0.125% + fentanyl
2 µg/mL at 10 mL/hr
Outcomes VAS pain scores, sensory level (pin prick) and motor block assessed at onset of analgesia,
60 min and then at 90 min intervals. Incidence of hypotension (no definition), nausea and
pruritus noted. Data on labour progress including cervical dilatation, use and maximum
dose of oxytocin and mode of delivery
Neonatal assessment of weight, gender and Apgar scores.
Notes USA.
Funded solely from institutional and departmental sources.
Risk of bias
Random sequence generation (selection Unclear risk Stated, “sequentially numbered, opaque,
bias) shuffled envelopes”, but randomisation
method not stated
Allocation concealment (selection bias) Low risk Stated, “sequentially numbered, opaque,
shuffled envelopes”.

Tsen 1999 (Continued)
Blinding (performance bias and detection Low risk Double-blinded, in epidural group the
bias) spinal needle placed without puncturing
All outcomes the dura and “dosed” with an empty syringe
to blind any observers to the technique be-
ing used
Incomplete outcome data (attrition bias) Low risk There is no loss to follow-up.
All outcomes
ported.
Van de Velde 1999
Methods Randomisation: method not stated “110 healthy women....participated in this prospec-
tive and randomised clinical trial”
Blinding: both mother and outcome assessor were blinded.
Criteria for rescue analgesia: if pain relief inadequate (VAS > 25 mm) PCEA lockout
time reduced from 15 min to 10 min and additional epidural boluses given manually as
needed
No losses to follow-up and data from all participants were used in statistical analysis
Participants Inclusions: 110 women ASA 1 or 2, > 36 weeks with singleton, vertex fetus. Cervical
dilatation 2 to 7 cm. No other sedative or analgesic drugs given
Exclusions: VAS < 60 mm at analgesia request. Substance-abusing parturients were ex-
cluded
Interventions Epidural (n = 55): 15 mL/kg crystalloid preload over 15 min. Bolus 10 mL bupivacaine
0.125% + sufentanil 0.75 µg/mL + epinephrine 1.25 µg/mL. Then PCEA connected at
first request for additional analgesia. PCEA bolus 4 mL of same solution with lockout
time 15 min
CSE (n = 55): 15 mL/kg crystalloid preload given over 15 min. Single space, needle-
through-needle, lateral position. IT injection bupivacaine 2.5 mg + sufentanil 1.5 µg
+ epinephrine 2.5 µg. Then immediately 10 mL saline administered down epidural
catheter. On request for additional analgesia, PCEA connected as for the epidural group
Outcomes Maternal heart rate, blood pressure and VAS for pain recorded. Onset time (VAS < 25
mm or reduced by > 50% from baseline). Incidence of side effects noted. Hypotension
defined as reduction of mean arterial pressure of > 20%. Sensory and motor block
assessed. Mode of delivery and fetal heart rate changes recorded. Maternal satisfaction
noted.
Neonatal assessment by Apgar scores at 1 and 5 min and umbilical artery pH
Notes Belgium.

Van de Velde 1999 (Continued)
Risk of bias

bias)
Blinding (performance bias and detection Low risk Both women and outcome assessor were
bias) blinded (second anaesthetist entered the
All outcomes room after the completion of the puncture
and was unaware of group assignment

All outcomes
ported.
Vernis 2004
Methods Randomisation: method not stated, “a prospective double-blind randomised study” and
“parturients were randomly included into 1 of 2 study groups, in a blind fashion.”
Blinding: midwife performing analgesia assessments and women both blinded
Participants Inclusions: 113 healthy women 18 to 40 years, 3 to 6 cm dilatation in active labour, >
37 weeks’ gestation, singleton, vertex
Exclusions: contraindications to regional, pre-eclampsia, psychological, IV opioid ad-
ministration, labour ’unduly complicated’, after-hours
No. lost to follow-up: 1 from ED group.
Interventions Epidural (n = 60): 0.125% bupivacaine plus sufentanil 7.5 µg, with adrenaline, volume
based on height, 4 mL initially as test dose. 5 mL 0.125% bupivacaine given if analgesia
inadequate at 15 min. PCEA commenced immediately
CSE (n = 54): needle-through-needle with 2.5 mg bupivacaine plus 5 µg sufentanil. Test
dose and initial ED followed by PCEA after return of pain
PCEA: bupivacaine 0.125% plus sufentanil 0.25 µg/mL; 4 mL bolus with 10 minute
lock-out
Outcomes Maternal: median time from injection to VAS (0 to 100) less than or equal to 30,
satisfaction, dural tap, PDPH and blood patch requirement, major complications, mode
of delivery
Notes France.

Vernis 2004 (Continued)
Risk of bias

bias)
Allocation concealment (selection bias) Low risk Stated, “parturients were randomly in-
cluded into one of the two study groups in
a blind fashion.”
Blinding (performance bias and detection Unclear risk Stated, “prospective double blind study,”
bias) no other information
All outcomes
Incomplete outcome data (attrition bias) Low risk Only 1 patient excluded from epidural
All outcomes group, no loss to follow-up
ported.
Other bias Unclear risk The study was stopped early (after 113
women rather than 128 that were originally
intended because of presumed incidence of
adverse effects from CSE)
Zeidan 2004
Methods Randomisation: random number table; “randomised in a double blinded manner”

Participants Inclusions: 104 women, ASA 1 to 2, requesting epidural, singleton, nulliparous, 36 to

41 weeks’ gestation, < 4 cm dilatation
Exclusions: multiple pregnancies, estimated fetal weight < 2500 gm, ED contraindicated,
suspected fetal abnormalities, IV analgesics within the previous hour
No. lost to follow-up: 3 in CSE group due to protocol violation; 1 in ED group withdrew
Interventions Epidural (n = 51): 1000 mL Ringer’s preload, left lateral; 10 to 20 mL 0.0625% (6.25
to 12.5 mg) bupivacaine plus fentanyl 15 to 30 µg
CSE (n = 50): preload as above: 1.25 mg bupivacaine plus fentanyl 25 µg
Subsequent management same in both groups: ED infusion commenced subsequently
at patient request of bupivacaine 0.0625% plus fentanyl 1.5 µg/mL, initial 3 mL bolus
followed by 6 to 10 mL/hr
Outcomes Maternal: VAS pain score at 0, 5, 10, 15 and 30 minutes; additional analgesic inter-
ventions required, satisfaction, mobilisation, known dural tap, PDPH and blood patch-
ing; adverse events needing treatment - hypotension, respiratory depression, nausea and
vomiting, pruritus; major complications, mode of delivery

Zeidan 2004 (Continued)
Fetal/neonatal: number admitted to the neonatal unit.
Notes Saudi Arabia.

Table 4 not in published paper.
Risk of bias
Random sequence generation (selection Low risk Stated, “using random number table”.
bias)
Blinding (performance bias and detection Unclear risk Stated, “double blinded”, no other infor-
bias) mation.
All outcomes
Incomplete outcome data (attrition bias) Low risk 2 women from CSE group were excluded
All outcomes because of protocol deviation, 1 patient
from the epidural group chose to discon-
tinue her participation. No loss to follow-
up
reported.
ASA: American Society of Anesthesiologists

BFSE: mixture of bupivacaine, fentanyl, sodium bicarbonate and epinephrine
BMI: body mass index
bpm: beats per minute
cm: centimetre
CSE: combined spinal-epidural
CSF: cerebrospinal fluid
CTG: cardiotography
ED: epidural
hr: hour
IJOA: International Journal of Anesthesiology
IT: intrathecal
IV: intravenous
LA: local anaesthetic
LSCS: lower segment caesarean section
µg: microgram
mg: milligram
min: minute
mL: millilitre

NaHCO3: sodium bicarbonate
no.: number
PCEA: patient-controlled epidural analgesia
PDPH: post dural puncture headache
SBP: systolic blood pressure
SpO2: saturation of oxygen
VAS: visual analogue score
Characteristics of excluded studies [ordered by study ID]
Study Reason for exclusion
Backus 1996 There were treatment differences within the groups depending on the degree of cervical dilatation more or less
than 5 cm
Camann 1992 All 24 women in this study had an intrathecal, an epidural and an intravenous injection. Only 1 of the 3
injections contained the active drug, namely sufentanil 10 µg, with the other 2 injections containing saline.
The route of sufentanil delivery depended on the group allocation. As all women received a CSE technique, it
was felt this did not constitute a direct comparison of CSE with epidural and, therefore, this study was excluded
from the review
Camann 1998 All 100 women entered into the study received an intrathecal injection. In 6 of the 9 groups the intrathecal
injection contained sufentanil 2, 5 or 10 µg. The remaining 3 groups received an injection of saline 2 mL. All
100 women also received an epidural bolus containing either bupivacaine or saline. Although the inclusion
of groups receiving only saline in the intrathecal injection allowed for complete double-blinding, it led to all
women technically receiving a CSE. As a result it was decided that this was not therefore a comparison of CSE
with epidural analgesia and the study was excluded
Cascio 1996 This study looked only at maternal catecholamine levels and did not address any of our outcomes
Collis 1995 Although this study was described as randomised and blinded, the women receiving CSE analgesia were assessed
for motor weakness and in the absence of motor block were allowed to walk if they wished. Women in the
epidural group were not assessed in this way and were not encouraged to mobilise
Collis 1999a All women received CSE analgesia.
Collis 1999b All women received CSE analgesia.
Cooper 2010 Although this is one of the COMET cluster of reports, this study specifically deals with comparisons involving
low-dose epidurals with traditional epidurals and hence is not relevant to this review
D’Angelo 1994 All women in the ’epidural’ group received an intrathecal injection of saline 2 mL enabling both mother and
operator to be blinded to treatment group allocation. However, this means that all women in the trial technically
received a CSE and so this study was excluded from analysis
Dresner 1999 All data relating to motor block and analgesic efficacy were collected retrospectively and took the form of
subjective maternal assessments on the first day postpartum. Intrapartum assessments were made by midwives
not blinded to treatment allocation. Assessments by the women were potentially biased as subjects were not

(Continued)
blinded either. In addition, 50 women withdrawn from the study for a variety of reasons were excluded from
all statistical analysis
Finegold 2003 Abstract only. Methodological quality unclear in relation to randomisation, allocation concealment, blinding
and attrition. No data presented against stated review outcomes
Fogel 1999 Excluded as treatment not the same for all participants within each group. Boluses of drugs given differed
according cervical dilatation
Groves 1995 Only addressed the rate of progress of labour which was not one of outcomes. No other information presented
is able to be analysed against our outcomes
Harsten 1997 All women received a CSE.
Kassapidis 1997 Study looked only at umbilical cord blood flow which was not one of outcomes
Leighton 1996 Women were not randomised for group allocation. CSE or epidural analgesia was provided on the basis of
patient request
Nageotte 1997 Like the Collis paper, here women who received CSE analgesia were treated differently with regard to mobili-
sation. There were 2 CSE groups in this study, 1 where mobilisation was encouraged and 1 where walking was
actively discouraged
Nielson 1996 Women were not randomised with regard to group allocation. “The type of anaesthetic technique used was
based on patient request, anesthesiologist’s preference and obstetrician’s choice”
Norris 1994 The women in this study were not randomised with regard to the type of analgesia they received. Allocation
was based on patient request
Norris 2001 This is stated to be “quasi-randomised”, with randomisation actually being in relation to day of week and no
allocation concealment. Treatments varied within groups at undefined operator discretion
Pan 1996 A very small study with insufficient detail regarding randomisation, allocation concealment, blinding and
outcome measurement for inclusion
Patel 2003b This is a dose-ranging study investigating minimum local analgesic requirements for epidural bupivacaine after
CSE or epidural, which was not in our stated outcomes for inclusion
Pham 1996 The 40 women entered into the study were randomly allocated to 1 of 2 groups. Those in the sufentanil group
received intrathecal sufentanil 10 µg followed by an epidural bolus of saline. The women in the bupivacaine
group received an intrathecal injection of saline 2 mL followed by an epidural bolus 12 mL bupivacaine 0.25%.
As all women in the study had a CSE technique performed, albeit with saline delivered as one of the injections
in each case, this study was excluded from data analysis
Pinto 2000 Randomisation, allocation concealment, blinding and attrition are all unclear. The study is a comparison of 2
CSE techniques with an epidural control that is not valid for inclusion
Rosenfeld 1998 All women received a CSE.

(Continued)
Stocche 2001 Primary outcomes were not stated outcomes for this review.
Van de Velde 2004 All women received a dural puncture; the epidural control included 2 mL intrathecal saline
Characteristics of studies awaiting assessment [ordered by study ID]
Arya 2007
Methods
Participants
Interventions
Outcomes
Notes Abstract only. Information regarding the following is inadequate to determine classification: randomisation method,
allocation concealment, the reason for the large number excluded; missing data for Apgar scores, satisfaction and the
number that actually mobilised
Celik 2005
Methods
Participants
Interventions
Outcomes
Notes Poster only. Information regarding the following is inadequate to determine classification: randomisation method,
allocation concealment, the number originally allocated, the number lost to follow-up, the reason for the large number
excluded, missing data for Apgar scores, satisfaction and the actual numbers in each group for mode of delivery
de Souza 2009
Methods
Participants
Interventions
Outcomes

de Souza 2009 (Continued)
Notes Awaiting clarification of numerous methodological matters.
Gupta 2002
Methods
Participants
Interventions
Outcomes
Kayacan 2006
Methods
Participants
Interventions
Outcomes
Lee 2007
Methods
Participants
Interventions
Outcomes
Lee 2007a
Methods
Participants
Interventions

Lee 2007a (Continued)
Outcomes
Lian 2008
Methods
Participants
Interventions
Outcomes
Notes Abstract only. There is no mention of Ethics approval or consent. The randomisation and allocation processes are
not defined. There appears to have been a control group in which no analgesia was offered. There are no usable data
presented. Further information may enable inclusion
Mantha 2007
Methods
Participants
Interventions
Outcomes
Nakamura 2009
Methods
Participants
Interventions
Outcomes
Notes

Olmez 2003
Methods
Participants
Interventions
Outcomes
Notes Turkish; requires translation. Abstract is deficient in ethics approval and informed consent; there is no detail regarding
the processes of randomisation or allocation concealment, the inclusion and exclusion criteria and the data pertinent
to this review
Pascual 2011
Methods
Participants
Interventions
Outcomes
Notes
Pascual-Ramirez 2010
Methods
Participants
Interventions
Outcomes
Notes
Pascual-Ramirez 2011
Methods
Participants
Interventions
Outcomes
Notes

Patel 2012
Methods
Participants
Interventions
Outcomes
Notes
Salem 2007
Methods
Participants
Interventions
Outcomes
Sweed 2011
Methods
Participants
Interventions
Outcomes
Notes
Wilson 2011
Methods
Participants
Interventions
Outcomes
Notes

DATA AND ANALYSES
Comparison 1. Combined spinal-epidural versus traditional epidural
No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size
1 Time from first injection to 2 129 Mean Difference (IV, Fixed, 95% CI) -2.87 [-5.07, -0.67]
effective analgesia (minutes)
1.1 Opioid combined 2 129 Mean Difference (IV, Fixed, 95% CI) -2.87 [-5.07, -0.67]
spinal-epidural versus
traditional epidural
2 Number of women with effective 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
analgesia 10 minutes after first
injection
3 Need for rescue analgesia 1 42 Risk Ratio (M-H, Fixed, 95% CI) 0.31 [0.14, 0.70]
3.1 Combined spinal-epidural 1 42 Risk Ratio (M-H, Fixed, 95% CI) 0.31 [0.14, 0.70]
versus traditional epidural
4 Number of women satisfied with 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
analgesia
5 Number of women who mobilise 1 40 Risk Ratio (M-H, Fixed, 95% CI) 1.0 [0.91, 1.10]
6 Post dural puncture headache 3 188 Risk Ratio (M-H, Fixed, 95% CI) 3.78 [0.16, 89.09]
6.1 Opioid combined 3 188 Risk Ratio (M-H, Fixed, 95% CI) 3.78 [0.16, 89.09]
7 Known dural tap 3 842 Risk Ratio (M-H, Random, 95% CI) 2.47 [0.36, 17.12]
7.1 Combined spinal-epidural 1 704 Risk Ratio (M-H, Random, 95% CI) 0.34 [0.01, 8.20]
7.2 Opioid combined 2 138 Risk Ratio (M-H, Random, 95% CI) 6.14 [0.73, 51.83]
8 Number of women requiring 1 79 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
blood patch for post dural
puncture headache
9 Pruritus 6 370 Risk Ratio (M-H, Random, 95% CI) 7.34 [0.14, 375.82]
10 Urinary retention 1 704 Risk Ratio (M-H, Fixed, 95% CI) 0.86 [0.79, 0.95]
10.1 Combined 1 704 Risk Ratio (M-H, Fixed, 95% CI) 0.86 [0.79, 0.95]
11 Nausea/vomiting 6 370 Risk Ratio (M-H, Random, 95% CI) 1.48 [0.55, 3.95]
11.1 Combined 2 142 Risk Ratio (M-H, Random, 95% CI) 0.25 [0.03, 2.05]
12 Hypotension 6 1002 Risk Ratio (M-H, Fixed, 95% CI) 0.81 [0.64, 1.01]
13 Respiratory depression 3 178 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
14 Headache (any) 1 79 Risk Ratio (M-H, Fixed, 95% CI) 1.03 [0.07, 15.83]
15 Sedation 1 79 Risk Ratio (M-H, Fixed, 95% CI) 1.03 [0.46, 2.31]
16 Labour augmentation required 3 883 Risk Ratio (M-H, Fixed, 95% CI) 0.95 [0.84, 1.09]
17 Augmentation after analgesia 1 100 Risk Ratio (M-H, Fixed, 95% CI) 0.5 [0.24, 1.06]
18 Normal delivery 7 1074 Risk Ratio (M-H, Random, 95% CI) 1.03 [0.90, 1.18]
19 Instrumental delivery 6 1015 Risk Ratio (M-H, Fixed, 95% CI) 0.81 [0.67, 0.97]
20 Caesarean section 6 1015 Risk Ratio (M-H, Fixed, 95% CI) 1.06 [0.85, 1.32]

21 Umbilical arterial pH 1 55 Mean Difference (IV, Fixed, 95% CI) -0.02 [-0.06, 0.02]
21.1 Opioid combined 1 55 Mean Difference (IV, Fixed, 95% CI) -0.02 [-0.06, 0.02]
22 Umbilical venous pH 1 55 Mean Difference (IV, Fixed, 95% CI) -0.03 [-0.06, -0.00]
22.1 Opioid combined 1 55 Mean Difference (IV, Fixed, 95% CI) -0.03 [-0.06, -0.00]
23 Umbilical cord pH 0 0 Mean Difference (IV, Fixed, 95% CI) 0.0 [0.0, 0.0]
24 Apgar score < 7 at 5 minutes 3 842 Risk Ratio (M-H, Fixed, 95% CI) 2.10 [0.63, 6.97]
26 Number admitted to neonatal 1 704 Risk Ratio (M-H, Fixed, 95% CI) 0.63 [0.29, 1.37]
unit
Comparison 2. Combined spinal-epidural versus low-dose epidural
No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size
1 Time from first injection to 5 461 Mean Difference (IV, Random, 95% CI) -5.42 [-7.26, -3.59]
effective analgesia (minutes)
1.1 Combined spinal-epidural 4 421 Mean Difference (IV, Random, 95% CI) -5.73 [-7.99, -3.48]
versus low-dose epidural
1.2 Opioid combined 1 40 Mean Difference (IV, Random, 95% CI) -4.24 [-6.17, -2.31]
spinal-epidural versus low-dose
epidural
2 Number of women with effective 1 101 Risk Ratio (M-H, Fixed, 95% CI) 1.94 [1.49, 2.54]
analgesia 10 minutes after first
injection
3 Need for rescue analgesia 9 1645 Risk Ratio (M-H, Fixed, 95% CI) 0.99 [0.80, 1.23]
spinal-epidural versus test local
anaesthetic/opioid epidural
3.3 Null combined 1 248 Risk Ratio (M-H, Fixed, 95% CI) 1.38 [0.64, 2.98]
epidural
4 Number of women satisfied with 7 520 Risk Ratio (M-H, Random, 95% CI) 1.01 [0.98, 1.05]
analgesia
epidural
5 Number of women who mobilise 7 1200 Risk Ratio (M-H, Random, 95% CI) 1.02 [0.90, 1.15]
6 Post dural puncture headache 9 701 Risk Ratio (M-H, Fixed, 95% CI) 1.68 [0.42, 6.81]
epidural
7 Known dural tap 6 1326 Risk Ratio (M-H, Random, 95% CI) 1.01 [0.16, 6.37]
7.3 Null combined 1 251 Risk Ratio (M-H, Random, 95% CI) 1.95 [0.18, 21.26]
epidural
8 Number of women requiring 7 531 Risk Ratio (M-H, Fixed, 95% CI) 2.22 [0.51, 9.64]
blood patch for post dural
puncture headache
epidural
9 Pruritus 11 959 Risk Ratio (M-H, Random, 95% CI) 1.80 [1.22, 2.65]

epidural
10 Urinary retention 4 964 Risk Ratio (M-H, Random, 95% CI) 0.96 [0.69, 1.35]
epidural
epidural
11 Nausea/vomiting 7 539 Risk Ratio (M-H, Random, 95% CI) 0.97 [0.65, 1.45]
epidural
epidural
12 Hypotension 14 2040 Risk Ratio (M-H, Random, 95% CI) 1.35 [0.89, 2.04]
epidural
12.3 Null combined 1 230 Risk Ratio (M-H, Random, 95% CI) 1.01 [0.71, 1.45]
epidural
13 Respiratory depression 5 375 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
epidural
epidural
14 Headache (any) 1 110 Risk Ratio (M-H, Fixed, 95% CI) 0.14 [0.01, 2.70]
epidural
15 Sedation 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
16 Labour augmentation required 6 1285 Risk Ratio (M-H, Fixed, 95% CI) 1.00 [0.88, 1.13]
epidural

epidural
epidural
17 Augmentation after analgesia 0 0 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
18 Normal delivery 12 1672 Risk Ratio (M-H, Fixed, 95% CI) 0.98 [0.92, 1.06]
epidural
epidural
epidural
19 Instrumental delivery 11 1612 Risk Ratio (M-H, Fixed, 95% CI) 1.07 [0.88, 1.30]
epidural
epidural
epidural
20 Caesarean section 15 1960 Risk Ratio (M-H, Fixed, 95% CI) 0.98 [0.82, 1.16]
epidural
epidural
epidural
21 Umbilical arterial pH 4 306 Mean Difference (IV, Random, 95% CI) -0.00 [-0.03, 0.03]

21.1 Combined 3 264 Mean Difference (IV, Random, 95% CI) -0.01 [-0.04, 0.02]
epidural
21.2 Opioid combined 1 42 Mean Difference (IV, Random, 95% CI) 0.04 [-0.03, 0.11]
epidural
22 Umbilical venous pH 2 85 Mean Difference (IV, Fixed, 95% CI) 0.03 [-5.95, 0.07]
22.1 Combined 1 43 Mean Difference (IV, Fixed, 95% CI) 0.02 [-0.04, 0.08]
epidural
22.2 Opioid combined 1 42 Mean Difference (IV, Fixed, 95% CI) 0.04 [-0.00, 0.08]
epidural
23 Umbilical cord pH 1 110 Mean Difference (IV, Fixed, 95% CI) -0.02 [-0.05, 0.01]
23.1 Combined 1 110 Mean Difference (IV, Fixed, 95% CI) -0.02 [-0.05, 0.01]
epidural
epidural
epidural
epidural
26 Number admitted to neonatal 3 852 Risk Ratio (M-H, Fixed, 95% CI) 0.77 [0.34, 1.73]
unit
epidural

Analysis 1.1. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 1 Time from
first injection to effective analgesia (minutes).
Review: Combined spinal-epidural versus epidural analgesia in labour
Comparison: 1 Combined spinal-epidural versus traditional epidural
Outcome: 1 Time from first injection to effective analgesia (minutes)
Mean Mean
Study or subgroup CSE Epidural Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
1 Opioid combined spinal-epidural versus traditional epidural

Ngamprasertwong 2007 25 7.8 (4.3) 25 10.2 (5.1) 70.9 % -2.40 [ -5.01, 0.21 ]
Roux 1999 39 8 (11) 40 12 (7) 29.1 % -4.00 [ -8.08, 0.08 ]
Total (95% CI) 64 65 100.0 % -2.87 [ -5.07, -0.67 ]

Heterogeneity: Chi2 = 0.42, df = 1 (P = 0.52); I2 =0.0%
Test for overall effect: Z = 2.55 (P = 0.011)
Test for subgroup differences: Not applicable
-10 -5 0 5 10
Favours CSE Favours epidural
Analysis 1.3. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 3 Need for
rescue analgesia.
Outcome: 3 Need for rescue analgesia
Study or subgroup CSE Epidural Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
1 Combined spinal-epidural versus traditional epidural

Gomez 2001 5/21 16/21 100.0 % 0.31 [ 0.14, 0.70 ]
Total (95% CI) 21 21 100.0 % 0.31 [ 0.14, 0.70 ]

Total events: 5 (CSE), 16 (Epidural)
Heterogeneity: not applicable
0.1 0.2 0.5 1 2 5 10


Analysis 1.5. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 5 Number of
women who mobilise.
Outcome: 5 Number of women who mobilise

Cortes 2007 20/20 20/20 100.0 % 1.00 [ 0.91, 1.10 ]
Total (95% CI) 20 20 100.0 % 1.00 [ 0.91, 1.10 ]

0.1 0.2 0.5 1 2 5 10

Favours epidural Favours CSE

Analysis 1.6. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 6 Post dural
puncture headache.
Outcome: 6 Post dural puncture headache
Study or subgroup CSE Epidural Risk Ratio Risk Ratio


Caldwell 1994 1/26 0/33 3.78 [ 0.16, 89.09 ]
Ngamprasertwong 2007 0/25 0/25 0.0 [ 0.0, 0.0 ]
Roux 1999 0/39 0/40 0.0 [ 0.0, 0.0 ]
Total (95% CI) 90 98 3.78 [ 0.16, 89.09 ]

0.01 0.1 1 10 100


Analysis 1.7. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 7 Known dural
tap.
Outcome: 7 Known dural tap

M- M-
H,Random,95% H,Random,95%
n/N n/N CI CI
COMET 2001a 0/351 1/353 31.2 % 0.34 [ 0.01, 8.20 ]
Subtotal (95% CI) 351 353 31.2 % 0.34 [ 0.01, 8.20 ]

Caldwell 1994 1/26 0/33 31.8 % 3.78 [ 0.16, 89.09 ]
Roux 1999 4/39 0/40 37.0 % 9.23 [ 0.51, 165.84 ]
Subtotal (95% CI) 65 73 68.8 % 6.14 [ 0.73, 51.83 ]

Heterogeneity: Tau2 = 0.0; Chi2 = 0.17, df = 1 (P = 0.68); I2 =0.0%
Total (95% CI) 416 426 100.0 % 2.47 [ 0.36, 17.12 ]
Heterogeneity: Tau2 = 0.47; Chi2 = 2.38, df = 2 (P = 0.30); I2 =16%
Test for subgroup differences: Chi2 = 2.20, df = 1 (P = 0.14), I2 =55%
0.001 0.01 0.1 1 10 100 1000


Analysis 1.8. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 8 Number of
women requiring blood patch for post dural puncture headache.
Outcome: 8 Number of women requiring blood patch for post dural puncture headache
Study or subgroup Treatment Control Risk Ratio Risk Ratio


Roux 1999 0/39 0/40 0.0 [ 0.0, 0.0 ]
Total (95% CI) 39 40 0.0 [ 0.0, 0.0 ]

Total events: 0 (Treatment), 0 (Control)
Test for overall effect: Z = 0.0 (P < 0.00001)
Test for subgroup differences: Chi2 = 0.0, df = -1 (P = 0.0), I2 =0.0%
0.1 0.2 0.5 1 2 5 10


Analysis 1.9. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 9 Pruritus.
Outcome: 9 Pruritus

M- M-
n/N n/N CI CI
Gomez 2001 11/21 2/21 5.50 [ 1.38, 21.86 ]
Tsen 1999 0/50 0/50 0.0 [ 0.0, 0.0 ]
Subtotal (95% CI) 71 71 5.50 [ 1.38, 21.86 ]

Caldwell 1994 13/26 1/33 16.50 [ 2.31, 118.07 ]
Cortes 2007 0/20 0/20 0.0 [ 0.0, 0.0 ]
Roux 1999 39/39 35/40 1.14 [ 1.01, 1.29 ]
Subtotal (95% CI) 110 118 8.35 [ 0.02, 3322.35 ]

Heterogeneity: Tau2 = 27.01; Chi2 = 82.47, df = 2 (P<0.00001); I2 =98%
Total (95% CI) 181 189 7.34 [ 0.14, 375.82 ]
Test for subgroup differences: Chi2 = 0.02, df = 1 (P = 0.89), I2 =0.0%
0.001 0.01 0.1 1 10 100 1000


Analysis 1.10. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 10 Urinary
retention.
Outcome: 10 Urinary retention


COMET 2001a 239/351 278/353 100.0 % 0.86 [ 0.79, 0.95 ]
Total (95% CI) 351 353 100.0 % 0.86 [ 0.79, 0.95 ]

0.1 0.2 0.5 1 2 5 10


Analysis 1.11. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 11
Nausea/vomiting.
Outcome: 11 Nausea/vomiting

M- M-
n/N n/N CI CI
Gomez 2001 1/21 4/21 0.25 [ 0.03, 2.05 ]
Tsen 1999 0/50 0/50 0.0 [ 0.0, 0.0 ]
Subtotal (95% CI) 71 71 0.25 [ 0.03, 2.05 ]

Caldwell 1994 13/26 5/33 3.30 [ 1.35, 8.07 ]
Cortes 2007 0/20 0/20 0.0 [ 0.0, 0.0 ]
Roux 1999 14/39 13/40 1.10 [ 0.60, 2.04 ]
Subtotal (95% CI) 110 118 1.97 [ 0.77, 5.05 ]

Total (95% CI) 181 189 1.48 [ 0.55, 3.95 ]
0.01 0.1 1 10 100


Hypotension.
Outcome: 12 Hypotension


COMET 2001a 92/342 115/349 0.82 [ 0.65, 1.03 ]
Gomez 2001 0/21 0/21 0.0 [ 0.0, 0.0 ]
Tsen 1999 0/50 0/50 0.0 [ 0.0, 0.0 ]
Subtotal (95% CI) 413 420 0.82 [ 0.65, 1.03 ]

Cortes 2007 0/20 0/20 0.0 [ 0.0, 0.0 ]
Roux 1999 0/39 2/40 0.21 [ 0.01, 4.14 ]
Subtotal (95% CI) 84 85 0.56 [ 0.12, 2.53 ]

Total (95% CI) 497 505 0.81 [ 0.64, 1.01 ]
0.5 0.7 1 1.5 2


Respiratory depression.
Outcome: 13 Respiratory depression


Caldwell 1994 0/26 0/33 0.0 [ 0.0, 0.0 ]
Cortes 2007 0/20 0/20 0.0 [ 0.0, 0.0 ]
Roux 1999 0/39 0/40 0.0 [ 0.0, 0.0 ]
Total (95% CI) 85 93 0.0 [ 0.0, 0.0 ]

Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
0.1 0.2 0.5 1 2 5 10


Analysis 1.14. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 14 Headache
(any).
Outcome: 14 Headache (any)
Study or subgroup Treatment Control Risk Ratio Weight Risk Ratio


Roux 1999 1/39 1/40 100.0 % 1.03 [ 0.07, 15.83 ]
Total (95% CI) 39 40 100.0 % 1.03 [ 0.07, 15.83 ]

0.01 0.1 1 10 100

Analysis 1.15. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 15 Sedation.
Outcome: 15 Sedation


Roux 1999 9/39 9/40 100.0 % 1.03 [ 0.46, 2.31 ]
Total (95% CI) 39 40 100.0 % 1.03 [ 0.46, 2.31 ]

0.1 0.2 0.5 1 2 5 10


Analysis 1.16. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 16 Labour
augmentation required.
Outcome: 16 Labour augmentation required


COMET 2001a 113/351 120/353 59.0 % 0.95 [ 0.77, 1.17 ]
Tsen 1999 40/50 43/50 21.2 % 0.93 [ 0.78, 1.11 ]
Subtotal (95% CI) 401 403 80.3 % 0.94 [ 0.80, 1.11 ]

Roux 1999 39/39 40/40 19.7 % 1.00 [ 0.95, 1.05 ]
Subtotal (95% CI) 39 40 19.7 % 1.00 [ 0.95, 1.05 ]

Total (95% CI) 440 443 100.0 % 0.95 [ 0.84, 1.09 ]
Heterogeneity: Chi2 = 3.68, df = 2 (P = 0.16); I2 =46%
0.1 0.2 0.5 1 2 5 10


Augmentation after analgesia.
Outcome: 17 Augmentation after analgesia


Tsen 1999 8/50 16/50 100.0 % 0.50 [ 0.24, 1.06 ]
Total (95% CI) 50 50 100.0 % 0.50 [ 0.24, 1.06 ]

0.1 0.2 0.5 1 2 5 10


Analysis 1.18. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 18 Normal
delivery.
Outcome: 18 Normal delivery

M- M-
n/N n/N CI CI
COMET 2001a 150/351 124/353 32.8 % 1.22 [ 1.01, 1.47 ]
Gomez 2001 11/21 12/21 5.6 % 0.92 [ 0.53, 1.59 ]
Tsen 1999 34/50 33/50 18.8 % 1.03 [ 0.78, 1.36 ]
Subtotal (95% CI) 422 424 57.1 % 1.14 [ 0.98, 1.32 ]

Caldwell 1994 14/26 23/33 9.1 % 0.77 [ 0.51, 1.18 ]
Cortes 2007 12/20 11/20 5.9 % 1.09 [ 0.64, 1.86 ]
Ngamprasertwong 2007 11/25 9/25 3.7 % 1.22 [ 0.62, 2.42 ]
Roux 1999 29/39 33/40 24.2 % 0.90 [ 0.71, 1.14 ]
Subtotal (95% CI) 110 118 42.9 % 0.92 [ 0.76, 1.10 ]

Total (95% CI) 532 542 100.0 % 1.03 [ 0.90, 1.18 ]
0.1 0.2 0.5 1 2 5 10


Instrumental delivery.
Outcome: 19 Instrumental delivery


COMET 2001a 102/351 131/353 76.6 % 0.78 [ 0.63, 0.97 ]
Gomez 2001 6/21 7/21 4.1 % 0.86 [ 0.35, 2.12 ]
Tsen 1999 8/50 8/50 4.7 % 1.00 [ 0.41, 2.46 ]
Subtotal (95% CI) 422 424 85.4 % 0.80 [ 0.65, 0.98 ]

Cortes 2007 4/20 8/20 4.7 % 0.50 [ 0.18, 1.40 ]
Roux 1999 7/39 5/40 2.9 % 1.44 [ 0.50, 4.14 ]
Subtotal (95% CI) 84 85 14.6 % 0.85 [ 0.52, 1.37 ]

Total (95% CI) 506 509 100.0 % 0.81 [ 0.67, 0.97 ]
0.1 0.2 0.5 1 2 5 10


Analysis 1.20. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 20 Caesarean
section.
Outcome: 20 Caesarean section


COMET 2001a 99/351 98/353 84.5 % 1.02 [ 0.80, 1.29 ]
Gomez 2001 4/21 2/21 1.7 % 2.00 [ 0.41, 9.77 ]
Tsen 1999 8/50 9/50 7.8 % 0.89 [ 0.37, 2.12 ]
Subtotal (95% CI) 422 424 94.0 % 1.02 [ 0.82, 1.28 ]

Cortes 2007 4/20 1/20 0.9 % 4.00 [ 0.49, 32.72 ]
Roux 1999 3/39 2/40 1.7 % 1.54 [ 0.27, 8.71 ]
Subtotal (95% CI) 84 85 6.0 % 1.58 [ 0.65, 3.87 ]

Total (95% CI) 506 509 100.0 % 1.06 [ 0.85, 1.32 ]
0.1 0.2 0.5 1 2 5 10


Analysis 1.21. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 21 Umbilical
arterial pH.
Outcome: 21 Umbilical arterial pH
Mean Mean

Caldwell 1994 26 7.24 (0.1) 29 7.26 (0.05) 100.0 % -0.02 [ -0.06, 0.02 ]
Total (95% CI) 26 29 100.0 % -0.02 [ -0.06, 0.02 ]

-0.5 -0.25 0 0.25 0.5

Analysis 1.22. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 22 Umbilical
venous pH.
Outcome: 22 Umbilical venous pH
Mean Mean

Caldwell 1994 26 7.33 (0.05) 29 7.36 (0.05) 100.0 % -0.03 [ -0.06, 0.00 ]
Total (95% CI) 26 29 100.0 % -0.03 [ -0.06, 0.00 ]

-0.5 -0.25 0 0.25 0.5


Analysis 1.24. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 24 Apgar
score < 7 at 5 minutes.
Outcome: 24 Apgar score < 7 at 5 minutes


Caldwell 1994 1/26 1/33 1.27 [ 0.08, 19.34 ]
COMET 2001a 7/351 3/353 2.35 [ 0.61, 9.00 ]
Roux 1999 0/39 0/40 0.0 [ 0.0, 0.0 ]
Total (95% CI) 416 426 2.10 [ 0.63, 6.97 ]

0.01 0.1 1 10 100


Analysis 1.25. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 25 Apgar
score < 8 at 5 minutes.


COMET 2001a 7/351 3/353 100.0 % 2.35 [ 0.61, 9.00 ]
Total (95% CI) 351 353 100.0 % 2.35 [ 0.61, 9.00 ]

0.1 0.2 0.5 1 2 5 10

Analysis 1.26. Comparison 1 Combined spinal-epidural versus traditional epidural, Outcome 26 Number
admitted to neonatal unit.
Outcome: 26 Number admitted to neonatal unit


COMET 2001a 10/351 16/353 100.0 % 0.63 [ 0.29, 1.37 ]
Total (95% CI) 351 353 100.0 % 0.63 [ 0.29, 1.37 ]

0.1 0.2 0.5 1 2 5 10


Analysis 2.1. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 1 Time from first
injection to effective analgesia (minutes).
Comparison: 2 Combined spinal-epidural versus low-dose epidural
Outcome: 1 Time from first injection to effective analgesia (minutes)
Mean Mean
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
1 Combined spinal-epidural versus low-dose epidural

Cohen 2006 68 8.4 (6.8) 68 15.6 (6.7) 19.0 % -7.20 [ -9.47, -4.93 ]
Kartawiadi 1996 25 4 (2) 25 10.4 (2.5) 23.8 % -6.40 [ -7.65, -5.15 ]
Nickells 2000 61 10 (5.7) 64 12.1 (6.5) 19.6 % -2.10 [ -4.24, 0.04 ]
Van de Velde 1999 55 5.43 (2.7) 55 12.77 (9.76) 17.0 % -7.34 [ -10.02, -4.66 ]
Subtotal (95% CI) 209 212 79.4 % -5.73 [ -7.99, -3.48 ]

2 Opioid combined spinal-epidural versus low-dose epidural
Sezer 2007 20 5.26 (1.15) 20 9.5 (4.26) 20.6 % -4.24 [ -6.17, -2.31 ]
Subtotal (95% CI) 20 20 20.6 % -4.24 [ -6.17, -2.31 ]

Total (95% CI) 229 232 100.0 % -5.42 [ -7.26, -3.59 ]
-100 -50 0 50 100


Analysis 2.2. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 2 Number of
women with effective analgesia 10 minutes after first injection.
Outcome: 2 Number of women with effective analgesia 10 minutes after first injection


Zeidan 2004 50/50 26/51 100.0 % 1.94 [ 1.49, 2.54 ]
Total (95% CI) 50 51 100.0 % 1.94 [ 1.49, 2.54 ]

0.1 0.2 0.5 1 2 5 10


Analysis 2.3. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 3 Need for
rescue analgesia.
Outcome: 3 Need for rescue analgesia


Cohen 2006 5/73 0/68 10.26 [ 0.58, 182.06 ]
COMET 2001a 80/351 86/350 0.93 [ 0.71, 1.21 ]
Goodman 2006 2/50 3/50 0.67 [ 0.12, 3.82 ]
Hepner 2000 0/26 0/24 0.0 [ 0.0, 0.0 ]
Nickells 2000 9/69 9/73 1.06 [ 0.45, 2.51 ]
Price 1998 15/45 18/48 0.89 [ 0.51, 1.54 ]
Zeidan 2004 0/50 0/51 0.0 [ 0.0, 0.0 ]
Subtotal (95% CI) 664 664 0.97 [ 0.77, 1.21 ]

2 Opioid combined spinal-epidural versus test local anaesthetic/opioid epidural
Dunn 1998 0/35 1/34 0.32 [ 0.01, 7.69 ]
Subtotal (95% CI) 35 34 0.32 [ 0.01, 7.69 ]

3 Null combined spinal-epidural versus low-dose epidural
Thomas 2005 14/125 10/123 1.38 [ 0.64, 2.98 ]
Subtotal (95% CI) 125 123 1.38 [ 0.64, 2.98 ]

Total (95% CI) 824 821 0.99 [ 0.80, 1.23 ]
0.01 0.1 1 10 100


women satisfied with analgesia.
Outcome: 4 Number of women satisfied with analgesia

M- M-
n/N n/N CI CI

Bhagwat 2008 30/30 30/30 17.0 % 1.00 [ 0.94, 1.07 ]
Hepner 2000 25/26 19/24 2.6 % 1.21 [ 0.98, 1.51 ]
Kartawiadi 1996 32/32 31/31 17.8 % 1.00 [ 0.94, 1.06 ]
Van de Velde 1999 53/55 48/55 8.1 % 1.10 [ 0.99, 1.24 ]
Vernis 2004 53/54 58/59 21.3 % 1.00 [ 0.95, 1.05 ]
Zeidan 2004 42/42 42/42 22.6 % 1.00 [ 0.96, 1.05 ]
Subtotal (95% CI) 239 241 89.4 % 1.02 [ 0.97, 1.06 ]

Sezer 2007 20/20 20/20 10.6 % 1.00 [ 0.91, 1.10 ]
Subtotal (95% CI) 20 20 10.6 % 1.00 [ 0.91, 1.10 ]

Total (95% CI) 259 261 100.0 % 1.01 [ 0.98, 1.05 ]
0.1 0.2 0.5 1 2 5 10


women who mobilise.
Outcome: 5 Number of women who mobilise

M- M-
n/N n/N CI CI

Cohen 2006 32/68 41/68 11.9 % 0.78 [ 0.57, 1.07 ]
COMET 2001a 133/351 128/350 23.2 % 1.04 [ 0.85, 1.26 ]
Parry 1998 27/30 27/30 26.5 % 1.00 [ 0.84, 1.18 ]
Price 1998 21/45 28/48 8.4 % 0.80 [ 0.54, 1.19 ]
Zeidan 2004 33/50 31/51 13.2 % 1.09 [ 0.81, 1.46 ]
Subtotal (95% CI) 544 547 83.2 % 0.98 [ 0.88, 1.09 ]

Breen 1999 20/21 13/19 11.7 % 1.39 [ 1.01, 1.92 ]
Dunn 1998 17/35 14/34 5.1 % 1.18 [ 0.70, 2.00 ]
Subtotal (95% CI) 56 53 16.8 % 1.33 [ 1.01, 1.75 ]

Total (95% CI) 600 600 100.0 % 1.02 [ 0.90, 1.15 ]
0.1 0.2 0.5 1 2 5 10


Analysis 2.6. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 6 Post dural
puncture headache.
Outcome: 6 Post dural puncture headache


Hepner 2000 0/26 0/24 0.0 [ 0.0, 0.0 ]
Kartawiadi 1996 2/32 1/31 1.94 [ 0.18, 20.30 ]
Parry 1998 0/30 0/30 0.0 [ 0.0, 0.0 ]
Price 1998 0/45 0/48 0.0 [ 0.0, 0.0 ]
Van de Velde 1999 0/55 0/55 0.0 [ 0.0, 0.0 ]
Vernis 2004 2/54 0/59 5.45 [ 0.27, 111.13 ]
Zeidan 2004 0/50 0/51 0.0 [ 0.0, 0.0 ]
Subtotal (95% CI) 292 298 3.06 [ 0.50, 18.69 ]

Dunn 1998 0/35 1/34 0.32 [ 0.01, 7.69 ]
Subtotal (95% CI) 35 34 0.32 [ 0.01, 7.69 ]

Abouleish 1991 0/20 0/22 0.0 [ 0.0, 0.0 ]
Subtotal (95% CI) 20 22 0.0 [ 0.0, 0.0 ]

Total (95% CI) 347 354 1.68 [ 0.42, 6.81 ]
0.001 0.01 0.1 1 10 100 1000


Analysis 2.7. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 7 Known dural
tap.
Outcome: 7 Known dural tap

M- M-
n/N n/N CI CI

COMET 2001a 0/351 3/350 0.14 [ 0.01, 2.75 ]
Hepner 2000 0/26 0/24 0.0 [ 0.0, 0.0 ]
Nickells 2000 0/69 0/73 0.0 [ 0.0, 0.0 ]
Vernis 2004 1/54 0/59 3.27 [ 0.14, 78.67 ]
Subtotal (95% CI) 500 506 0.65 [ 0.03, 14.14 ]

Dunn 1998 0/35 0/34 0.0 [ 0.0, 0.0 ]
Subtotal (95% CI) 35 34 0.0 [ 0.0, 0.0 ]

Thomas 2005 2/127 1/124 1.95 [ 0.18, 21.26 ]
Subtotal (95% CI) 127 124 1.95 [ 0.18, 21.26 ]

Total (95% CI) 662 664 1.01 [ 0.16, 6.37 ]
0.001 0.01 0.1 1 10 100 1000


women requiring blood patch for post dural puncture headache.
Outcome: 8 Number of women requiring blood patch for post dural puncture headache
Study or subgroup Treatment Control Risk Ratio Risk Ratio


Kartawiadi 1996 2/32 0/31 4.85 [ 0.24, 97.11 ]
Price 1998 0/45 0/48 0.0 [ 0.0, 0.0 ]
Zeidan 2004 0/50 0/51 0.0 [ 0.0, 0.0 ]
Subtotal (95% CI) 127 130 4.85 [ 0.24, 97.11 ]

Dunn 1998 0/35 1/34 0.32 [ 0.01, 7.69 ]
Subtotal (95% CI) 35 34 0.32 [ 0.01, 7.69 ]

Abouleish 1991 0/20 0/22 0.0 [ 0.0, 0.0 ]
Hepner 2000 0/26 0/24 0.0 [ 0.0, 0.0 ]
Vernis 2004 2/54 0/59 5.45 [ 0.27, 111.13 ]
Subtotal (95% CI) 100 105 5.45 [ 0.27, 111.13 ]

Total (95% CI) 262 269 2.22 [ 0.51, 9.64 ]
Heterogeneity: Chi2 = 2.02, df = 2 (P = 0.36); I2 =1%
0.001 0.01 0.1 1 10 100 1000


Analysis 2.9. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 9 Pruritus.
Outcome: 9 Pruritus

M- M-
n/N n/N CI CI

Cohen 2006 42/68 38/68 1.11 [ 0.83, 1.47 ]
Goodman 2006 15/43 3/41 4.77 [ 1.49, 15.26 ]
Hepner 2000 24/26 21/24 1.05 [ 0.87, 1.27 ]
Kartawiadi 1996 17/32 8/31 2.06 [ 1.04, 4.06 ]
Price 1998 25/45 26/48 1.03 [ 0.71, 1.48 ]
Skupski 2009 32/64 19/63 1.66 [ 1.06, 2.60 ]
Van de Velde 1999 27/55 20/55 1.35 [ 0.87, 2.10 ]
Vernis 2004 34/54 7/59 5.31 [ 2.57, 10.96 ]
Zeidan 2004 0/50 0/51 0.0 [ 0.0, 0.0 ]
Subtotal (95% CI) 437 440 1.60 [ 1.13, 2.28 ]

Abouleish 1991 6/20 1/22 6.60 [ 0.87, 50.18 ]
Sezer 2007 12/20 0/20 25.00 [ 1.58, 395.48 ]
Subtotal (95% CI) 40 42 10.53 [ 2.05, 53.99 ]

Total (95% CI) 477 482 1.80 [ 1.22, 2.65 ]
0.01 0.1 1 10 100


Analysis 2.10. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 10 Urinary
retention.
Outcome: 10 Urinary retention

M- M-
n/N n/N CI CI

Cohen 2006 15/68 23/68 22.2 % 0.65 [ 0.37, 1.14 ]
COMET 2001a 239/351 218/350 52.8 % 1.09 [ 0.98, 1.22 ]
Price 1998 5/45 9/48 9.3 % 0.59 [ 0.21, 1.63 ]
Subtotal (95% CI) 464 466 84.3 % 0.86 [ 0.55, 1.34 ]

Abouleish 1991 9/16 7/18 15.7 % 1.45 [ 0.70, 2.98 ]
Subtotal (95% CI) 16 18 15.7 % 1.45 [ 0.70, 2.98 ]

Total (95% CI) 480 484 100.0 % 0.96 [ 0.69, 1.35 ]
0.1 0.2 0.5 1 2 5 10


Analysis 2.11. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 11
Nausea/vomiting.
Outcome: 11 Nausea/vomiting

M- M-
n/N n/N CI CI

Hepner 2000 3/26 2/24 1.38 [ 0.25, 7.59 ]
Skupski 2009 12/64 13/63 0.91 [ 0.45, 1.84 ]
Van de Velde 1999 11/55 13/55 0.85 [ 0.42, 1.72 ]
Zeidan 2004 0/50 0/51 0.0 [ 0.0, 0.0 ]
Subtotal (95% CI) 195 193 0.91 [ 0.56, 1.47 ]

Dunn 1998 7/35 7/34 0.97 [ 0.38, 2.48 ]
Subtotal (95% CI) 35 34 0.97 [ 0.38, 2.48 ]

Abouleish 1991 4/20 0/22 9.86 [ 0.56, 172.33 ]
Sezer 2007 4/20 4/20 1.00 [ 0.29, 3.45 ]
Subtotal (95% CI) 40 42 2.25 [ 0.23, 22.01 ]

Total (95% CI) 270 269 0.97 [ 0.65, 1.45 ]
0.001 0.01 0.1 1 10 100 1000


Analysis 2.12. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 12 Hypotension.
Outcome: 12 Hypotension

M- M-
n/N n/N CI CI
Cohen 2006 0/68 3/68 0.14 [ 0.01, 2.71 ]
COMET 2001a 92/342 82/337 1.11 [ 0.86, 1.43 ]
Goodman 2006 7/43 0/41 14.32 [ 0.84, 242.95 ]
Hepner 2000 4/26 4/24 0.92 [ 0.26, 3.29 ]
Kartawiadi 1996 0/32 0/31 0.0 [ 0.0, 0.0 ]
Nickells 2000 2/61 0/64 5.24 [ 0.26, 107.02 ]
Parry 1998 0/30 0/30 0.0 [ 0.0, 0.0 ]
Price 1998 0/45 0/48 0.0 [ 0.0, 0.0 ]
Skupski 2009 26/64 11/63 2.33 [ 1.26, 4.30 ]
Van de Velde 1999 3/55 3/55 1.00 [ 0.21, 4.74 ]
Vernis 2004 8/54 0/59 18.55 [ 1.10, 313.82 ]
Zeidan 2004 0/50 0/51 0.0 [ 0.0, 0.0 ]
Subtotal (95% CI) 870 871 1.59 [ 0.85, 2.96 ]

Dunn 1998 0/35 0/34 0.0 [ 0.0, 0.0 ]
Subtotal (95% CI) 35 34 0.0 [ 0.0, 0.0 ]

Thomas 2005 37/107 42/123 1.01 [ 0.71, 1.45 ]
Subtotal (95% CI) 107 123 1.01 [ 0.71, 1.45 ]

0.01 0.1 1 10 100

(Continued . . . )

(. . .Continued)
M- M-
n/N n/N CI CI
Total (95% CI) 1012 1028 1.35 [ 0.89, 2.04 ]
0.01 0.1 1 10 100

Analysis 2.13. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 13 Respiratory
depression.
Outcome: 13 Respiratory depression

Hepner 2000 0/26 0/24 0.0 [ 0.0, 0.0 ]
Vernis 2004 0/54 0/59 0.0 [ 0.0, 0.0 ]
Zeidan 2004 0/50 0/51 0.0 [ 0.0, 0.0 ]
Subtotal (95% CI) 130 134 0.0 [ 0.0, 0.0 ]

Dunn 1998 0/35 0/34 0.0 [ 0.0, 0.0 ]
Subtotal (95% CI) 35 34 0.0 [ 0.0, 0.0 ]

0.1 0.2 0.5 1 2 5 10

(Continued . . . )

(. . . Continued)
Abouleish 1991 0/20 0/22 0.0 [ 0.0, 0.0 ]
Subtotal (95% CI) 20 22 0.0 [ 0.0, 0.0 ]

Total (95% CI) 185 190 0.0 [ 0.0, 0.0 ]
0.1 0.2 0.5 1 2 5 10

Analysis 2.14. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 14 Headache
(any).
Outcome: 14 Headache (any)


Van de Velde 1999 0/55 3/55 100.0 % 0.14 [ 0.01, 2.70 ]
Total (95% CI) 55 55 100.0 % 0.14 [ 0.01, 2.70 ]

0.001 0.01 0.1 1 10 100 1000


Analysis 2.16. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 16 Labour
augmentation required.
Outcome: 16 Labour augmentation required


COMET 2001a 113/351 120/350 47.8 % 0.94 [ 0.76, 1.16 ]
Nickells 2000 5/69 9/73 3.5 % 0.59 [ 0.21, 1.67 ]
Zeidan 2004 35/50 33/51 13.0 % 1.08 [ 0.82, 1.42 ]
Subtotal (95% CI) 470 474 64.3 % 0.95 [ 0.80, 1.13 ]

Dunn 1998 8/35 5/34 2.0 % 1.55 [ 0.56, 4.28 ]
Subtotal (95% CI) 35 34 2.0 % 1.55 [ 0.56, 4.28 ]

Abouleish 1991 1/20 2/22 0.8 % 0.55 [ 0.05, 5.61 ]
Subtotal (95% CI) 20 22 0.8 % 0.55 [ 0.05, 5.61 ]

Thomas 2005 83/107 89/123 32.9 % 1.07 [ 0.92, 1.24 ]
Subtotal (95% CI) 107 123 32.9 % 1.07 [ 0.92, 1.24 ]

Total (95% CI) 632 653 100.0 % 1.00 [ 0.88, 1.13 ]
0.01 0.1 1 10 100


Analysis 2.18. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 18 Normal
delivery.
Outcome: 18 Normal delivery


COMET 2001a 150/351 150/350 29.4 % 1.00 [ 0.84, 1.18 ]
Hepner 2000 20/26 17/24 3.5 % 1.09 [ 0.78, 1.51 ]
Kartawiadi 1996 22/32 24/31 4.8 % 0.89 [ 0.66, 1.20 ]
Parry 1998 18/30 18/30 3.5 % 1.00 [ 0.66, 1.51 ]
Price 1998 20/45 23/48 4.3 % 0.93 [ 0.60, 1.44 ]
Van de Velde 1999 46/55 46/55 9.0 % 1.00 [ 0.85, 1.18 ]
Vernis 2004 41/54 45/59 8.4 % 1.00 [ 0.81, 1.22 ]
Zeidan 2004 36/50 35/51 6.8 % 1.05 [ 0.81, 1.35 ]
Subtotal (95% CI) 643 648 69.6 % 1.00 [ 0.91, 1.09 ]

Dunn 1998 28/35 28/34 5.6 % 0.97 [ 0.77, 1.22 ]
Subtotal (95% CI) 35 34 5.6 % 0.97 [ 0.77, 1.22 ]

Abouleish 1991 16/20 18/22 3.4 % 0.98 [ 0.73, 1.31 ]
Sezer 2007 16/20 16/20 3.1 % 1.00 [ 0.73, 1.36 ]
Subtotal (95% CI) 40 42 6.5 % 0.99 [ 0.80, 1.22 ]

Thomas 2005 83/107 101/123 18.4 % 0.94 [ 0.83, 1.08 ]
Subtotal (95% CI) 107 123 18.4 % 0.94 [ 0.83, 1.08 ]

0.1 0.2 0.5 1 2 5 10

(Continued . . . )

(. . . Continued)
Total (95% CI) 825 847 100.0 % 0.98 [ 0.92, 1.06 ]
0.1 0.2 0.5 1 2 5 10

Analysis 2.19. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 19 Instrumental
delivery.
Outcome: 19 Instrumental delivery


COMET 2001a 102/351 98/350 1.04 [ 0.82, 1.31 ]
Hepner 2000 2/26 1/24 1.85 [ 0.18, 19.08 ]
Kartawiadi 1996 7/32 5/31 1.36 [ 0.48, 3.82 ]
Price 1998 13/45 15/48 0.92 [ 0.50, 1.72 ]
Van de Velde 1999 7/55 6/55 1.17 [ 0.42, 3.25 ]
Vernis 2004 9/54 8/59 1.23 [ 0.51, 2.96 ]
Zeidan 2004 3/50 3/51 1.02 [ 0.22, 4.82 ]
Subtotal (95% CI) 613 618 1.06 [ 0.87, 1.30 ]

0.01 0.1 1 10 100

(Continued . . . )

(. . . Continued)
Dunn 1998 2/35 2/34 0.97 [ 0.14, 6.51 ]
Subtotal (95% CI) 35 34 0.97 [ 0.14, 6.51 ]

Abouleish 1991 0/20 0/22 0.0 [ 0.0, 0.0 ]
Sezer 2007 0/20 0/20 0.0 [ 0.0, 0.0 ]
Subtotal (95% CI) 40 42 0.0 [ 0.0, 0.0 ]

Thomas 2005 10/107 9/123 1.28 [ 0.54, 3.03 ]
Subtotal (95% CI) 107 123 1.28 [ 0.54, 3.03 ]

Total (95% CI) 795 817 1.07 [ 0.88, 1.30 ]
0.01 0.1 1 10 100


Analysis 2.20. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 20 Caesarean
section.
Outcome: 20 Caesarean section


Abrao 2009 13/41 13/36 7.2 % 0.88 [ 0.47, 1.64 ]
Bhagwat 2008 1/30 0/30 0.3 % 3.00 [ 0.13, 70.83 ]
COMET 2001a 99/351 102/350 52.9 % 0.97 [ 0.77, 1.22 ]
Goodman 2006 4/43 5/41 2.6 % 0.76 [ 0.22, 2.64 ]
Hepner 2000 4/26 6/24 3.2 % 0.62 [ 0.20, 1.92 ]
Kartawiadi 1996 3/32 2/31 1.1 % 1.45 [ 0.26, 8.11 ]
Price 1998 12/45 10/48 5.0 % 1.28 [ 0.61, 2.67 ]
Skupski 2009 11/64 12/63 6.3 % 0.90 [ 0.43, 1.89 ]
Van de Velde 1999 2/55 3/55 1.6 % 0.67 [ 0.12, 3.84 ]
Vernis 2004 4/54 6/59 3.0 % 0.73 [ 0.22, 2.44 ]
Zeidan 2004 8/50 9/51 4.6 % 0.91 [ 0.38, 2.16 ]
Subtotal (95% CI) 791 788 87.6 % 0.95 [ 0.79, 1.14 ]

Dunn 1998 5/35 4/34 2.1 % 1.21 [ 0.36, 4.14 ]
Subtotal (95% CI) 35 34 2.1 % 1.21 [ 0.36, 4.14 ]

Abouleish 1991 4/20 4/22 2.0 % 1.10 [ 0.32, 3.83 ]
Sezer 2007 4/20 4/20 2.1 % 1.00 [ 0.29, 3.45 ]
Subtotal (95% CI) 40 42 4.0 % 1.05 [ 0.44, 2.53 ]

0.1 0.2 0.5 1 2 5 10

(Continued . . . )

(. . . Continued)
Thomas 2005 14/107 13/123 6.3 % 1.24 [ 0.61, 2.52 ]
Subtotal (95% CI) 107 123 6.3 % 1.24 [ 0.61, 2.52 ]

Total (95% CI) 973 987 100.0 % 0.98 [ 0.82, 1.16 ]
0.1 0.2 0.5 1 2 5 10


Analysis 2.21. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 21 Umbilical
arterial pH.
Outcome: 21 Umbilical arterial pH
Mean Mean
N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI

Hepner 2000 22 7.33 (0.1) 17 7.28 (0.1) 14.9 % 0.05 [ -0.01, 0.11 ]
Patel 2003a 62 7.23 (0.01) 53 7.25 (0.01) 45.7 % -0.02 [ -0.02, -0.02 ]
Van de Velde 1999 55 7.25 (0.1) 55 7.27 (0.1) 26.6 % -0.02 [ -0.06, 0.02 ]
Subtotal (95% CI) 139 125 87.2 % -0.01 [ -0.04, 0.02 ]

Abouleish 1991 20 7.26 (0.09) 22 7.22 (0.14) 12.8 % 0.04 [ -0.03, 0.11 ]
Subtotal (95% CI) 20 22 12.8 % 0.04 [ -0.03, 0.11 ]

Total (95% CI) 159 147 100.0 % 0.00 [ -0.03, 0.03 ]
-0.5 -0.25 0 0.25 0.5


venous pH.
Outcome: 22 Umbilical venous pH
Mean Mean

Hepner 2000 23 7.34 (0.1) 20 7.32 (0.1) 32.4 % 0.02 [ -0.04, 0.08 ]
Subtotal (95% CI) 23 20 32.4 % 0.02 [ -0.04, 0.08 ]

Abouleish 1991 20 7.33 (0.04) 22 7.29 (0.09) 67.6 % 0.04 [ 0.00, 0.08 ]
Subtotal (95% CI) 20 22 67.6 % 0.04 [ 0.00, 0.08 ]

Total (95% CI) 43 42 100.0 % 0.03 [ 0.00, 0.07 ]
-0.01 -0.01 0 0.01 0.01


cord pH.
Outcome: 23 Umbilical cord pH
Mean Mean
Study or subgroup Treatment Control Difference Weight Difference

Van de Velde 1999 55 7.25 (0.07) 55 7.27 (0.07) 100.0 % -0.02 [ -0.05, 0.01 ]
Total (95% CI) 55 55 100.0 % -0.02 [ -0.05, 0.01 ]

-0.5 -0.25 0 0.25 0.5


Analysis 2.24. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 24 Apgar score
< 7 at 5 minutes.


Abrao 2009 0/41 0/36 0.0 [ 0.0, 0.0 ]
Bhagwat 2008 1/31 0/30 2.91 [ 0.12, 68.66 ]
COMET 2001a 7/351 10/350 0.70 [ 0.27, 1.81 ]
Hepner 2000 0/26 1/24 0.31 [ 0.01, 7.23 ]
Price 1998 0/45 1/48 0.36 [ 0.01, 8.50 ]
Van de Velde 1999 0/55 0/55 0.0 [ 0.0, 0.0 ]
Total (95% CI) 549 543 0.70 [ 0.31, 1.59 ]

0.01 0.1 1 10 100


Analysis 2.25. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 25 Apgar score
< 8 at 5 minutes.


COMET 2001a 7/351 10/350 0.70 [ 0.27, 1.81 ]
Kartawiadi 1996 1/32 0/31 2.91 [ 0.12, 68.81 ]
Parry 1998 0/30 0/30 0.0 [ 0.0, 0.0 ]
Vernis 2004 0/54 0/59 0.0 [ 0.0, 0.0 ]
Subtotal (95% CI) 467 470 0.80 [ 0.33, 1.97 ]

Abouleish 1991 1/20 0/22 3.29 [ 0.14, 76.33 ]
Subtotal (95% CI) 20 22 3.29 [ 0.14, 76.33 ]

Total (95% CI) 487 492 0.91 [ 0.39, 2.12 ]
0.01 0.1 1 10 100


Analysis 2.26. Comparison 2 Combined spinal-epidural versus low-dose epidural, Outcome 26 Number
admitted to neonatal unit.
Outcome: 26 Number admitted to neonatal unit


COMET 2001a 10/351 13/350 0.77 [ 0.34, 1.73 ]
Hepner 2000 0/26 0/24 0.0 [ 0.0, 0.0 ]
Zeidan 2004 0/50 0/51 0.0 [ 0.0, 0.0 ]
Total (95% CI) 427 425 0.77 [ 0.34, 1.73 ]

0.1 0.2 0.5 1 2 5 10

ADDITIONAL TABLES
Table 1. Epidural techniques used - initial dose and subsequent maintenance
INITIAL Nil Immediate Repeat Repeat Bolus/ Repeat PCEA

DOSE maintenance infusion boluses boluses infusion boluses
LA + opioid High-dose Low-dose LA Low-dose Low-dose

LA LA/opioid LA/opioid
Low-dose Abouleish
bupivacaine 1991
< 0.25%
Tra- Gomez 2001 COMET Thomas 2005

ditional dose 2001a
bupivacaine Ngamprasert- Cortes 2007
= 0.25% wong
2007
Tsen 1999

Table 1. Epidural techniques used - initial dose and subsequent maintenance (Continued)
Low- Parry 1998 Bhagwat 2008 Hepner 2000 Abrao 2009 Cohen 2006
dose bupiva- Patel 2003a COMET Medina 1994 Kartawiadi Price 1998
caine < 0. 2001a Zeidan 2004 1996 Sezer 2007
25% + opioid Goodman Nickells 2000 Van de Velde
2006 1999
Skupski 2009 Vernis 2004
Traditional Caldwell 1994 Roux 1999

dose bupiva-
caine + opi-
oid
Test ligno- Breen 1999

caine + opi- Dunn 1998
oid
Table 2. CSE techniques used - initial IT injection and subsequent epidural
CSE Nil epidural Immediate Immedi- Immediate Delay bolus/ Delayed bo- PCEA
technique infusion ate bolus/in- bolus/es infusion luses
fusion
IT
INJECTION
IT opioid Breen 1999 Ngamprasert- Caldwell 1994 Abouleish Sezer 2007

only Dunn 1998 wong 1991
2007 Cortes 2007
Roux 1999
IT LA + opi- Parry 1998 Bhagwat 2008 Gomez 2001 Hepner 2000 Abrao 2009 Cohen 2006
oid Patel 2003a Goodman Medina 1994 COMET Price 1998
2006 Tsen 1999 2001a Van de Velde
Skupski 2009 Zeidan 2004 Kartawiadi 1999
1996 Vernis 2004
Nickells 2000
IT nil Thomas 2005

IT: intrathecal

APPENDICES
Appendix 1. Methods used to assess trials included in previous versions of this review
Study identification
Types of studies to be considered for review included all published randomised controlled trials involving a comparison of combined
spinal-epidural (CSE) with epidural analgesia initiated for women in the first stage of labour. Trials were identified for inclusion by
three review authors independently. Details of reasons for exclusion of any trial considered for review have been clearly stated. If there
were any disagreements regarding inclusion of potentially eligible trials these were resolved by discussion and, if necessary, arbitration
by a fourth review author.
Quality assessment of included studies

• Three review authors independently assessed the quality of all relevant studies.
• Details of randomisation were recorded as satisfactory, unclear or unsatisfactory. Studies were excluded from the review if
randomisation was clearly unsatisfactory, e.g. by day of the week, case note number, date of birth, etc.
• Concealment of allocation was described as adequate, inadequate or unclear.
• Blinding of outcome assessments and the number of women lost to follow-up in included studies was noted.
Data extraction
• Data were extracted using a structured form that captured patient demographics (e.g. primipara/multipara), stage of labour, use
of oxytocics prior to regional technique.
• The technique and drug details of the CSE and the epidural groups were noted and classified.
• Three review authors independently extracted the data and differences resolved by referring to the original study.
Data analysis
• Dichotomous data were expressed as risk ratios.
• An intention-to-treat analysis was performed to include all randomised women where possible.
We assessed possible sources of heterogeneity by subgroup analyses and sensitivity analyses. The large diversity of both CSE and epidural
techniques used resulted in up to six separate subgroup analyses being conducted. The definition of these groups is covered in detail
under the ’Interventions’ section below. ’CSE’ groups consisted of both local anaesthetic and opioid, ’opioid CSE’ groups used only
opioids in the CSE, while the ’null CSE’ group consisted of studies with a spinal puncture but no intrathecal injection of drugs. ’Low-
dose’ epidurals used less than 0.25% bupivacaine or equivalent. Some epidural groups used only a test dose of local anaesthetic, i.e. a
relatively small dose at the time of initiating the block. Hence, separate analyses were performed for studies comparing:
• CSE with both traditional epidural regimens and also low-dose epidural techniques;
• other types of CSE regimens using an ’opioid only’ spinal component with both traditional and low-dose techniques and also
where only local anaesthetic as a test dose had been given.
Sensitivity analyses were performed by excluding trials that:
1. do not report comparable groups, e.g. with respect to parity, age, use of oxytocics prior to administration of the regional
technique; or
2. where outcomes have not been or may not have been properly blinded.
We tested for publication bias using the funnel plot visually.
We performed statistical analyses with the Review Manager software (RevMan 2008) for calculation of the treatment effect as represented
by either the random-effects or the fixed-effect models depending upon the status of heterogeneity.

WHAT’S NEW
Last assessed as up-to-date: 1 March 2012.
Date Event Description
31 January 2012 New search has been performed Search updated in September 2011 and nine new tri-
als identified. Eight new studies have been included
(Abrao 2009; Bhagwat 2008; Cohen 2006; Cortes
2007; Goodman 2006; Ngamprasertwong 2007; Sezer
2007; Skupski 2009) and one excluded (Cooper 2010)
.
We updated the search on 30 June 2012 and identi-
fied seven new reports for considertion at the next up-
date (Nakamura 2009; Pascual 2011; Pascual-Ramirez
2010; Pascual-Ramirez 2011; Patel 2012; Sweed 2011;
Wilson 2011) - see Characteristics of studies awaiting
classification.
The methods have been updated.
31 January 2012 New citation required but conclusions have not changed Review updated.
HISTORY
Protocol first published: Issue 4, 2001
Review first published: Issue 4, 2003
Date Event Description
1 September 2008 Amended Converted to new review format.
22 May 2007 New citation required and conclusions have changed Comparisons were restructured to be more clinically
relevant around combined spinal-epidural versus ei-
ther traditional or low-dose epidural techniques. With
this approach there appears to be little basis for recom-
mending one technique over the other with there now
being no difference in maternal satisfaction or other
key outcomes
31 December 2006 New search has been performed Search updated. An additional five studies were in-
cluded (Medina 1994; Patel 2003a; Thomas 2005;
Vernis 2004; Zeidan 2004).

CONTRIBUTIONS OF AUTHORS
Planning of review: Allan Cyna.
Writing of draft protocol: Allan Cyna.
Revision of draft protocol: Allan Cyna, Scott Simmons.
Retrieving papers for review: Damien Hughes, Scott Simmons.
Extracting data from reviewed papers: Damien Hughes, Scott Simmons, Alicia Dennis, Neda Taghizadeh
Checking data prior to entry on Review Manager: Damien Hughes, Scott Simmons, Alicia Dennis, Neda Taghizadeh
Checking data entry on Review Manager: Damien Hughes, Scott Simmons, Alicia Dennis.
Writing of draft review: Damien Hughes, Scott Simmons, Allan Cyna.
DECLARATIONS OF INTEREST
None known.
SOURCES OF SUPPORT
Internal sources
• No sources of support supplied
External sources
• Department of Health and Ageing, Australia.
DIFFERENCES BETWEEN PROTOCOL AND REVIEW

We have updated the methods to reflect the latest Cochrane Handbook (Higgins 2011).
INDEX TERMS
Medical Subject Headings (MeSH)

∗ Labor,Obstetric; Analgesia, Epidural [adverse effects; ∗ methods]; Analgesia, Obstetrical [adverse effects; ∗ methods]; Anesthesia,
Epidural [adverse effects; methods]; Anesthesia, Spinal [adverse effects; ∗ methods]; Randomized Controlled Trials as Topic

MeSH check words
Female; Humans; Pregnancy


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Combined spinal-epidural versus epidural analgesia in labour

Simmons SW, Taghizadeh N, Dennis AT, Hughes D, Cyna AM

Combined spinal-epidural versus epidural analgesia in labour (Review)

Combined spinal-epidural versus epidural analgesia in labour (Review) ii

Combined spinal-epidural versus epidural analgesia in labour

Editorial group: Cochrane Pregnancy and Childbirth Group.

PLAIN LANGUAGE SUMMARY

Combined spinal-epidural versus epidural analgesia in labour

Combined spinal-epidural versus epidural analgesia in labour (Review) 3

Combined spinal-epidural versus epidural analgesia in labour (Review) 4

Combined spinal-epidural versus epidural analgesia in labour (Review) 5

(5) Selective reporting (checking for reporting bias)

We described for each included study how we investigated the

Combined spinal-epidural versus epidural analgesia in labour (Review) 6

Data synthesis RESULTS

Combined spinal-epidural versus epidural analgesia in labour (Review) 7

Combined spinal-epidural versus epidural analgesia in labour (Review) 8

Combined spinal-epidural versus epidural analgesia in labour (Review) 9

Combined spinal-epidural versus epidural analgesia in labour (Review) 10

Combined spinal-epidural versus epidural analgesia in labour (Review) 11

Combined spinal-epidural versus epidural analgesia in labour (Review) 12

Combined spinal-epidural versus epidural analgesia in labour (Review) 13

Combined spinal-epidural versus epidural analgesia in labour (Review) 14

Combined spinal-epidural versus epidural analgesia in labour (Review) 15

2.8); urinary retention (Analysis 2.10); nausea/vomiting (Analysis

Combined spinal-epidural versus epidural analgesia in labour (Review) 16

Combined spinal-epidural versus epidural analgesia in labour (Review) 17

Combined spinal-epidural versus epidural analgesia in labour (Review) 24

Combined spinal-epidural versus epidural analgesia in labour (Review) 25

Characteristics of included studies [ordered by study ID]

Participants Inclusions: 62 women ASA 1 or 2 at term, with singleton cephalic fetus

Interventions Epidural (n = 22): bolus 10 mL bupivacaine 0.125%. Then as requested further 10 mL

Bias Authors’ judgement Support for judgement

Combined spinal-epidural versus epidural analgesia in labour (Review) 26

Other bias Low risk No other bias evident.

Methods Randomisation: a computer-generated random number series.

Interventions All women received 10 mL/kg crystalloid prior to epidural insertion

Combined spinal-epidural versus epidural analgesia in labour (Review) 27

Bias Authors’ judgement Support for judgement

Random sequence generation (selection Low risk Computer-generated random numbers is

Other bias Low risk No other bias evident.

Methods Randomisation: using a computer-generated randomisation list

Interventions All women received 10 mL/kg crystalloid prior to epidural insertion

Combined spinal-epidural versus epidural analgesia in labour (Review) 28

Bias Authors’ judgement Support for judgement

Random sequence generation (selection Low risk Used a computer-generated randomisation

Allocation concealment (selection bias) Unclear risk Not stated.

Methods Randomisation: computer-generated randomisation in blocks of 4 with allocation con-

Combined spinal-epidural versus epidural analgesia in labour (Review) 29

Bias Authors’ judgement Support for judgement

Random sequence generation (selection Low risk Computer-generated randomisation in

Other bias Low risk No other bias evident.

Combined spinal-epidural versus epidural analgesia in labour (Review) 30

Methods Randomisation: not stated. “Patients were randomly assigned...”.

Interventions Epidural: 33 women received epidural analgesia, initiated with 10 mL bupivacaine 0.

Bias Authors’ judgement Support for judgement

Random sequence generation (selection Low risk Randomisation was by computer-gener-

Combined spinal-epidural versus epidural analgesia in labour (Review) 31

Blinding (performance bias and detection Unclear risk Not stated.

Incomplete outcome data (attrition bias) Low risk No loss to follow-up.

Other bias Low risk No other bias evident.

Methods Parturients who requested epidural analgesia were randomised

Notes USA. Abstracts only: 2004, 2004 and 2006.